International journal of clinical pharmacology and therapeutics (INT J CLIN PHARM TH)

Publisher: Dustri-Verlag

Journal description

The International Journal of Clinical Pharmacology and Therapeutics appears monthly and publishes manuscripts containing original material with emphasis on the following topics: Clinical trials, Pharmacoepidemiology - Pharmacovigilance, Pharmacodynamics, Drug disposition and Pharmacokinetics, Quality assurance, Pharmacogenetics, Biotechnological drugs such as cytokines and recombinant antibiotics. Case reports on adverse reactions are also of interest.

Current impact factor: 1.22

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 1.223
2013 Impact Factor 1.044
2012 Impact Factor 1.2
2011 Impact Factor 1.183
2010 Impact Factor 1.189
2009 Impact Factor 1.381
2008 Impact Factor 1.299
2007 Impact Factor 1.281
2006 Impact Factor 1.361
2005 Impact Factor 1.755
2004 Impact Factor 1.414
2003 Impact Factor 0.923
2002 Impact Factor 1.471
2001 Impact Factor 1.351
2000 Impact Factor 1.222
1999 Impact Factor 0.871
1998 Impact Factor 0.77
1997 Impact Factor 0.519
1996 Impact Factor 0.828
1995 Impact Factor 0.607
1994 Impact Factor 0.424
1993 Impact Factor 0.37
1992 Impact Factor 0.756

Impact factor over time

Impact factor
Year

Additional details

5-year impact 1.17
Cited half-life 8.00
Immediacy index 0.24
Eigenfactor 0.00
Article influence 0.31
Website International Journal of Clinical Pharmacology & Therapeutics website
Other titles International journal of clinical pharmacology and therapeutics, Clinical pharmacology and therapeutics
ISSN 0946-1965
OCLC 29934177
Material type Periodical
Document type Journal / Magazine / Newspaper

Publisher details

Dustri-Verlag

  • Pre-print
    • Archiving status unclear
  • Post-print
    • Archiving status unclear
  • Conditions
    • We have contacted this publisher on multiple occasions, and have not been able to obtain a response to our enquiries. If you have any information on this publisher's policy, please submit an update using the form below.
  • Classification
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Object: The aim of this study was to investigate whether UGT1A1*6/*28 or ABCB1-3435C>T polymorphisms affect irinotecan-induced severe diarrhea and neutropenia in Chinese cancer patients. Methods: A total of 157 cancer patients was enrolled in this study and the genotypes of UGT1A1*6/*28 and ABCB1-3435C>T polymorphisms were analyzed by PCRSanger sequence. The relationship between UGT1A1*6/*28 and ABCB1-3435C>T polymorphisms and irinotecan induced severe diarrhea and neutropenia were analyzed. Results and conclusion: UGT1A1*6 and UGT1A1*28 polymorphisms were associated with severe neutropenia (p = 0.025, p = 0.022, respectively) but not diarrhea (p = 0.343, p = 0.185, respectively), and ABCB1- 3435C>T polymorphism was not associated with irinotecan induced severe toxicities (p = 0.457, p = 0.161, respectively).
    No preview · Article · Feb 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objectives: The objectives of this study were to construct a population pharmacokinetics model for dexmedetomidine used in Chinese adult patients with spinal anesthesia and to identify the key factors affecting the pharmacokinetics of dexmedetomidine. Methods: A total of 34 subjects (elderly group: n = 15; young group: n = 19) undergoing spinal anesthesia received dexmedetomidine with a loading dose of 0.5 μg×kg-1 for 10 minutes, followed by a maintenance dose of 0.5 μg×kg-1×h-1 for 50 minutes. Blood samples were collected until 10 hours after dosing. Laboratory and respiratory parameters, and dexmedetomidine concentrations were measured. A population pharmacokinetic model for dexmedetomidine was constructed using a nonlinear mixed effects model (NONMEM). Results: Pharmacokinetics of dexmedetomidine can be described by a three-compartment model. The respective typical values for clearance (CL), V1, V2, Q2, Q3, and V3 were 0.883 L×min-1, 17.6 L, 51.5 L, 2.37 L×min-1, 0.517 L×min-1, and 44.00 L. Alanine aminotransferase (ALT), age, and body weight were key factors affecting CL, V1, and V2, respectively. Conclusions: A three-compartment model can be used to describe the pharmacokinetics processing of dexmedetomidine for Chinese adult patients during spinal anesthesia. The population pharmacokinetic of dexmedetomidine was generally in line with results from previous studies.
    No preview · Article · Feb 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Background: To compare the effects and side effects of intrathecal ropivacaine supplemented with dexmedetomidine and fentanyl in hysteroscopic surgery under spinal anesthesia. Methods: Female patients (n = 108) undergoing operative hysteroscopic procedures under spinal anesthesia were randomly allocated to the following groups for subarachnoid drug delivery: R (n = 36) received 7.5 mg ropivacaine; RD (n = 36) received 7.5 mg ropivacaine plus 5 μg dexmedetomidine; RF (n = 36) received 7.5 mg ropivacaine plus 15 μg fentanyl. The onset and regression time of sensory and motor blockade, together with the postoperative analgesia and side effects were recorded. Results: There was no significant difference as to sensory and motor onset time between groups. RD had significantly longer sensory and motor blockade time than RF and R. The mean time of sensory regression to the S1 segment was 191.25 ± 40.24 minutes in RD, 149.86 ± 37.46 minutes in RF, and 139.44 ± 38.97 minutes in R (RD vs. R and RD vs. RF, p < 0.001). The regression time of motor blockade to Bromage score 0 was 146.31 ± 40.72 minutes in RD, 80.28 ± 41.18 minutes in RF, and 84.94 ± 26.11 minutes in R (RD vs. R and RD vs. RF, p < 0.001). RD produced similar analgesia effect with RF, (2 hour visual analog scale (VAS) was 0.00 ± 0.00 and 0.31 ± 0.79, respectively) better than the R group (1.35 ± 1.65, p < 0.005). No pruritus occurred in the RD group, while the rate was 36.1% in the RF group. However, the RD group produced milder postsurgical hypotension (RD vs. R and RD vs. RF, p < 0.05). Conclusion: Intrathecal dexmedetomidine (5 μg) produced prolonged motor and sensory blockade and less pruritus compared with fentanyl (15 μg) in hysteroscopic surgery.
    No preview · Article · Feb 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: This first-in-human, randomized, double-blind, placebo-controlled trial assessed the safety of NNC0114-0005, a human recombinant anti interleukin (IL)-21 monoclonal antibody, for the treatment of rheumatoid arthritis (RA). Methods and materials: Healthy male subjects (HS (n = 44)) and patients with active RA treated with methotrexate (n = 20) were randomized 3 : 1 to single IV or SC doses of NNC0114-0005 (0.0025 - 25 mg/kg) or placebo. Safety endpoints, pharmacokinetics, and pharmacodynamics were assessed over 12 weeks. Results: All study participants were analyzed. 37 AEs were reported in 21 NNC0114-0005-treated participants (44%) and 18 AEs in 10 placebo-treated participants (63%), with no dose-dependency. The most common AEs were headache and nasopharyngitis; there were no injection-site reactions Linear pharmacokinetics of NNC0114-0005 were indicated (mean terminal half-life, 2 - 3 weeks). Dose-dependent total IL-21 (free IL-21 and IL-21‒NNC0114-0005 complexes) accumulation was observed. Preliminary signs of reduced RA activity were observed with 25 mg/kg NNC0114-0005. Conclusions: Single doses of NNC0114-0005 (≤ 25 mg/kg IV; ≤ 4 mg/kg SC) were well tolerated in HS and patients with RA. Accumulation of IL-21-containing complexes suggests neutralization of the target cytokine. Based on this trial, further trials to explore the efficacy of anti-IL-21 were initiated.
    No preview · Article · Feb 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: Azithromycin (AZM) is widely used as a first-line treatment option for children with mycoplasma pneumonia. Although pharmacists perform medication counseling in the pediatric ward, children often experience vomiting as a result of oral AZM administration. Drugs that are administered rectally are generally considered to enter the circulation system without passing through the liver first. The aim of our study was to prepare an AZM suppository and investigate the pharmaceutical properties and well as pharmacokinetics of the rectal administration route in humans. Materials and methods: Five healthy volunteers were enrolled in the study. All subjects provided written informed consent before participating in the study. Subjects were randomly assigned to either oral administration of oral AZM 500-mg tablet or rectal administration of 125-mg, 250-mg, or 500-mg AZM suppository. Blood samples for preparation of serum were collected predose as well as at 1, 2, 3, 4, 6, 12, and 24 hours following the first rectal dose. Serum concentrations of AZM were determined by high-performance liquid chromatography (HPLC) with electrochemical detection. Results and conclusion: The bioavailability of the AZM suppository through rectal administration was 20.3% compared to oral administration. We hypothesize that the surface area where AZM is absorbed also affects the absorption by rectal administration. Although further investigation is necessary to improve the absorption of AZM by the rectum and to ensure safety in children, the AZM suppository may be an effective preparation in cases where oral administration is not tolerated.
    No preview · Article · Feb 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Purpose: Human multidrug and toxin extrusion member 1 (MATE1, SLC47A1) and Organic Cation Transporter 2 (OCT2, SLC22A2) play important roles in the renal elimination of various pharmacologic agents, including the anti-diabetic drug metformin. The goal of this study was to determine the association between metformin's pharmacokinetics and pharmacodynamics and the genetic variants of MATE1 (rs2289669) and OCT2 (rs316019) before and after treatment with the potential MATE inhibitor, ranitidine. Methods: We recruited 26 healthy Koreans balanced across the OCT2 and MATE1 genetic variants, and conducted a prospective clinical trial to investigate their effects on metformin's pharmacokinetics and pharmacodynamics before and after ranitidine treatment. Results: Neither MATE1 rs2289669 nor OCT2 rs316019 affected metformin's pharmacokinetics and pharmacodynamics before ranitidine treatment. However, the renal clearance of metformin was significantly higher (15.2%) after ranitidine treatment in the MATE1 GG group compared with the MATE1 GA + AA group. Only the effect of MATE1 on the renal clearance of metformin after ranitidine treatment was significant (b = -0.465, p ≤ 0.05) after including demographic data and the OCT2 genotype in the model. Conclusion: Our study suggests that MATE1 rs2289669 may be a significant determinant in the renal clearance of metformin in the case of transporter-mediated drug interactions.
    No preview · Article · Jan 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Purpose: The aim of this study was to investigate the sex-dependent difference in P-glycoprotein activity as measured by the probe drug talinolol. Methods: A randomized, single-blind, parallel study was carried out in 20 healthy male and 20 healthy female volunteers. The pharmacokinetics of talinolol were measured after single oral dosing of 50-mg tablet and the pharmacokinetic parameters for male and female subjects were compared after excluding the potential influence of P-gp genetic polymorphisms. Results: Talinolol AUC0-48h in the female subjects was 23.5% (p = 0.003) higher than that of male subjects. There was no significant sex difference in weight-corrected oral clearance, AUC, or other PK parameters. Conclusion: The AUC and other PK data of talinolol, corrected for body weight, did not differ between genders after oral administration. The observed sex difference in talinolol systemic exposure is of little clinical relevance. The overall activity of P-gp shows no sex-related difference.
    No preview · Article · Jan 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: To assess potentially inappropriate medications (PIMs) in elderly outpatients taking multiple medications. Methods: Invoicing data of the prescriptions and electronic medical records were used to apply the STOPP (screening tool of older people's prescriptions) criteria. Results: Three out of 4 patients included in the study received PIMs. The most common criteria found were: duplicate drug class prescriptions (n = 58 (17.4%)), long-term long-acting benzodiazepines (n = 54 (16.2%)), and acetylsalicylic acid with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event (n = 32 (9.6%)). Conclusion: Our results highlight the relevance of the systematic review of the pharmacological treatments in these patients.
    No preview · Article · Jan 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: To report of a case successful use of infliximab (IFX) and tacrolimus (TAC) in a patient with ulcerative colitis (UC). Case summary: A 22-year-old woman diagnosed with UC started treatment with azathioprine 2.5 mg/kg. After 3 years of therapy, she developed a severe relapse. A colonoscopy was performed showing diffuse continuous mucosal disease and multiple erosions (< 5 mm) with no signs of spontaneous bleeding. Treatment with IFX 5 mg/kg at weeks 0, 2, and 6 was started. After IFX induction, she remained with symptoms: six stools per day, as well as presenting bloody diarrhea, tenesmus, and no abdominal pain. An IFX dose intensification of 5 mg/kg every 6 weeks was prescribed. After 6 months of azathioprine plus IFX therapy, patient's clinical condition was improved: 3 - 4 stools per day, 20% of bloody diarrhea, tenesmus, and no abdominal pain. Her Mayo endoscopic subscore was 6.3 months later, and a severe relapse of ulcerative colitis was presented. The patient refused a surgical treatment. Azathioprine 2.5 mg/kg/day was suspended and TAC 0.2 mg/kg/day (12 mg/day) as a compassionate use was added to IFX dose intensification of 10 mg/kg every 8 weeks and mesalamine 800 mg 3 times daily. After the first month of combined therapy, the patient's clinical condition improved with no bloody stools and abdominal pain. After 6 months of combination therapy, the patient was in remission, with two stools per day, no tenesmus and no abdominal pain. Due to the patient's clinical remission, IFX was suspended. Tacrolimus was continued on 10 mg/day. After 6 months of TAC monotherapy, the patient continued without symptoms (1 - 2 normal stools per day). Conclusions: Based on our case, the combination therapy of IFX and TAC could be selected as an effective approach for the patients with UC refractory to IFX dose intensification plus AZA. However, further studies need to be performed to evaluate the efficacy of this combination therapy.
    No preview · Article · Jan 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: Since the 1960s, fentanyl has been used to replace morphine nd other opioids due to its higher potency in the treatment of acute pain; since the 1990s, it has also been administrated to control chronic pain by using transdermal fentanyl device system. It is crucial and of utmost importance and crucial to validate a sensitive method for the quantification of transdermal fentanyl in human plasma. Materials and methods: A rapid, simple and sensitive high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method has been established and validated for the determination of transdermal fentanyl in human plasma using fentanyl-D5 as an internal standard (IS). Following liquid-liquid extraction (LLE) with n-hexane, the extracts were separated on a Thermo Hypersil ODS(C18) column (2.1 × 150 mm i.d., 5 μm) interfaced with a triple-quadrupole tandem mass spectrometer using positive electrospray ionization. Results and conclusions: Quantification of fentanyl was carried out by multiple reaction monitoring (MRM) of the transitions at m/z 337.1→188.0 for fentanyl and 341.9→187.9 for IS. The lower limit of quantification was 9.75 pg×mL-1, and the test showed a linear range of 9.75 - 10,000 pg×mL-1. The validated method was subsequently applied to a bioequivalence (BE) study in 24 healthy Chinese volunteers by using transdermal fentanyl patches.
    No preview · Article · Jan 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: We previously reported the first case of piloerection in a patient receiving milnacipran hydrochloride (MLP). Here, we now present a second case of MLP-induced piloerection. We discuss this effect in terms of α1-adrenoceptor occupancy. Case summary: After the first case of MLP-induced piloerection, we monitored occurrence of piloerection in our patients taking MLP. In response to our interview, a 43-year-old woman who had been prescribed MLP by a psychiatrist for depression mentioned that piloerection occurred frequently all over her body, starting soon after initiation of MLP administration (50 mg/day). Although she was concerned at the time, she assumed it might be related to her depression or to coldness in winter. She also mentioned that the incidence of piloerection increased with MLP dose escalation. The piloerection disappeared after several months. Interestingly, the previous patient and the current patient are biological sisters. Discussion: Changes in α1-adrenoceptor occupancy by endogenous norepinephrine (as an index of the risk of piloerection) in the presence of MLP were estimated. The occupancy values increased with MLP dose escalation, in accordance with the patient's report of the phenomenon. other concomitant drugs, such as nortriptyline, had little effect. Since the two patients were sisters, genetic factors might influence the risk of piloerection. Conclusion: The incidence of piloerection appeared to increase with MLP dose escalation in this patient, who was the biological sister of the previously reported patient. Clinicians should recognize the possibility of MLPinduced piloerection in view of its potential impact on patients' quality of life and on drug compliance.
    No preview · Article · Jan 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objectives: To evaluate the pharmacokinetics of paroxetine controlledrelease tablets after single oral administrations and its safety profile in healthy Chinese subjects. Methods: This was a phase I, openlabel, single-dose, three-period crossover study in which 12 healthy subjects received single oral doses of 12.5, 25, 37.5 mg paroxetine controlled-release tablets with 10-day washout between doses. Serial venous blood samples were collected for 96 hours after study drug administration and analyzed with LC-MS/MS. Pharmacokinetic parameters of paroxetine were calculated using non-compartmental analysis with Win-Nonlin software. Results: The absorption of controlled-release paroxetine was delayed with a median tmax of 8 - 10 hours and the mean t1/2 was 12 - 14 hours across all doses. Over the dose range of 12.5 - 37.5 mg, the mean Cmax increased from 2.62 to 15.13 ng/mL and AUC0-∞ increased from 63.56 to 404.91 h×ng/mL. The 90% CI for the ratio of dose-normalized mean values of Cmax and AUC were not contained within the criteria limits, indicating a greater than doseproportional increase. All reported adverse events were considered to be mild. Conclusions: Plasma exposure of controlled-release paroxetine increased with dose escalation, but linear pharmacokinetics were not observed over the studied doses. Paroxetine controlled-release tablet was well tolerated in healthy Chinese subjects.
    No preview · Article · Jan 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: To assess the bioequivalence (BE) potential under fasting conditions between levothyroxine soft capsules and the European reference tablet formulation. Methods: Two studies were conducted to assess the BE potential as per European regulations. Study 1 was a two-way crossover BE study comparing a high strength of levothyroxine soft capsules versus levothyroxine tablets (200 μg), while study 2 was a three-way crossover dosage form proportionality study between low, medium, and high strengths of soft capsules. 70 healthy adult subjects participated in the two studies. Each treatment consisted of a 600-μg dose of levothyroxine sodium, administered under fasting conditions. Blood samples were collected for levothyroxine (T4) assay prior to dosing and up to 72 hours post dose. A washout of 35 days separated treatments in each study. Pharmacokinetics was assessed using noncompartmental methods. Results: A total of 61 subjects completed the studies. Baseline-adjusted total T4 ratios (test/reference) and 90% confidence intervals (CIs) between soft capsules and tablets were within 80.00 - 125.00%. Comparison of the three strengths of soft capsules indicated pharmacokinetic equivalence between them (ratios and 90% CIs were contained within 80.00 - 125.00%). Overall, levothyroxine sodium was well tolerated with all products when given as single oral doses of 600 μg, except for 1 serious adverse event of secondary bacteremia reported in study 2, deemed not to be related to treatment. Conclusion: Levothyroxine soft capsules meet BE criteria in terms of systemic exposure when compared to a European reference tablet under fasting conditions in healthy volunteers.
    No preview · Article · Jan 2016 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Purpose: For the past decades, the long-term results of renal allograft unchanged despite the development of immunology and drugs. The long-term use of a calcineurin-inhibitor (CNI) and medication nonadherence have become important issues affecting long-term results. The combination of the once-daily advagraf and sirolimus was proposed as a good alternative with such reasons. The purpose of this study was the analysis of the clinical advantages of oncedaily advagraf and sirolimus combination by decreasing the use of CNI and improving medication adherence in stable kidney recipients. Materials and methods: In this study, 34 patients who switched from their present medication to a once-daily advagraf and sirolimus combination at Korea University Anam Hospital from September 2011 to March 2013 were retrospectively reviewed for 24 months. Laboratory findings, clinical findings, and medication adherence were reviewed and analyzed Results: After conversion to the new regimen, renal function was slightly improved at 3 months, as evidenced by creatinine levels (p = 0.024) and eGFR (p < 0.001). Lipid profiles deteriorated throughout the study period. Serum fast glucose level and proteinuria increased significantly at 12 months but recovered at 24 months. On the Morisky-Green test (MGT) for medication adherence, there were adherent improvements of 23.33% after 12 months and 16.66% after 24 months. Conclusion: The once-daily advagraf and sirolimus combination can be a safe and effective regimen in stable kidney recipients as the study shows that the regimen improves renal function and medication adherence with controllable adverse effects of sirolimus.
    No preview · Article · Dec 2015 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: Clinicians demand for methods to monitor effects of direct anticoagulants in the emergency setting. We recently described a coagulation assay based on surface acoustic waves (SAW) technology, which quantifies anticoagulant effects by image processing. Here we describe the first step in miniaturizing this laboratory method and provide a portable prototype that contains the optical illumination and automatic on-board image processing. Methods: A device about the size of a shoebox was realized that contains the SAW-chip, the signal generator, the LED illumination, as well as the necessary lenses, aperture, and CCD sensor. The microspheres in the blood were mixed by SAW, and the movement of the microspheres was quantified by on-board image processing. Upon contact with activationinduced coagulation, this movement ceases, and coagulation times were measured and compared to the manual methods obtained by standard fluorescent microscopy. A major advantage of our method is the low amount of blood (~ 6 μL) necessary for testing. Results: Results from the prototype correlated accurately with manual methods (Pearson correlation coefficient r = 0.9644). SAW-induced clotting time under anticoagulant treatment with dabigatran or rivaroxaban was well correlated with physicochemically determined plasma concentrations of these DOACs in anticoagulated patients. Compared to manual alignment of the chip under the fluorescence microscope, the prototype had a lower coefficient of variation. Conclusions: The last evolution step towards a point-of-care (POC)-device would be the development of a cartridge (containing calcium chloride and fluorescent label) such that a drop of blood can be introduced into the reaction vessel by a fluid actuator system.
    No preview · Article · Dec 2015 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: To investigate the time-dose-response relationship of benvitimod cream after topical administration in patients with mild and moderate psoriasis vulgaris for dosage regimen exploring. Methods: 36 patients with mild and moderate psoriasis vulgaris were randomly assigned to receive 0.5%, 1.0%, 1.5%, and 0% (placebo) benvitimod cream of 30 g/1.7 m2 twice daily for 6 weeks. The primary efficacy outcome was the proportion of patients achieving more than 75% change of the psoriasis area and severity index (PASI 75) from baseline. A longitudinal Emax model was established using the NONMEM method, and then applied to try to find an appropriate dose for following trials. Results: In the final time-dose-response model, the primary outcome at week 6 of PASI 75 of the 0.5%, 1.0%, and 1.5% benvitimod cream was 31%, 63%, and 75%, respectively, demonstrating that the 1.0% benvitimod cream was an appropriate dose for the next trial. The time parameters of ET50 and ET90 were 15 and 69 days for 1.0% benvitimod cream, indicating that the maximum efficacy of PASI change rate was obtained at approximately week 10. The accuracy of PASI change rate by extrapolation prediction was limited at week 10, so the treatment period should be longer in future trials. Conclusions: The established dose-response model could well describe the relationship between PASI change rate and doses of benvitimod cream in patients with mild and moderate psoriasis vulgaris. This modeling approach may help choose 1.0% benvitimod cream twice daily as a dosage regimen in following clinical trials.
    No preview · Article · Dec 2015 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objectives: We aimed to describe and to evaluate the clinical and economic implications of pharmacists' interventions as members of the liver transplant team for hospitalized liver recipients. Methods: Retrospective descriptive and cost-benefit analysis of documented pharmacist interventions for hospitalized patients from January 2010 to June 2012 was conducted. The type of drug-related problems (DRPs) was categorized. The clinical significance of pharmacist interventions was rated using five scales by two professionals. The cost avoidance was estimated based on the probability that an adverse drug event (ADE) would have occurred without intervention using previously reported additional costs for ADE treatment. Results: A total of 1,880 interventions were documented for 420 liver transplant recipients. The most common DRP was "need additional drug therapy" (42.6%), followed by "dosage problems" (23.5%). The most common drug class addressed by intervention was antimicrobials (51.4%). Most interventions were rated as more than clinically "significant". Analysis showed that pharmacist activities related to potential ADE prevention had a clear cost-benefit with a net cost-benefit € 94,009 and a cost-benefit ratio of 3.8. Conclusion: This study demonstrated the positive impact of clinical pharmacists on the care of hospitalized liver transplant patients in terms of both clinical and economic outcomes.
    No preview · Article · Dec 2015 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: Omecamtiv mecarbil is a novel small molecule that directly activates cardiac myosin and increases cardiac contractility without increasing cardiac myocyte intracellular calcium. This study evaluated the relative bioavailability, food effect, and safety of several modified-release (MR) formulations of omecamtiv mecarbil. Methods: This was a phase 1, randomized, openlabel, 4-way crossover, incomplete blockdesign study evaluating 5 MR formulations of omecamtiv mecarbil vs. an immediaterelease (IR) formulation. Materials: Healthy subjects were randomized to 1 of 30 possible sequences: within each sequence, subjects were assigned to receive a single 25-mg dose of 2 of the 6 possible formulations in the fasting and/or fed states. Results: 65 subjects were screened and enrolled; 5 were replacement subjects. Pharmacokinetic and safety data were analyzed from 62 and 63 subjects in the fasting and fed states, respectively. Compared with the IR formulation, median tmax was longer (0.5 vs. 2 - 10 hours), and mean Cmax was lower for all 5 MR formulations (262 vs. 34 - 78 ng/mL); t1/2,z was similar (18 - 21 hours). The relative bioavailability was high (> 75%) for three MR formulations but lower (< 65%) for the other two. Overall, the effect of food on omecamtiv mecarbil pharmacokinetics was minimal for four of the MR formulations. The pharmacokinetics of the inactive metabolites M3 and M4 were similar across all formulations. Conclusions: The relative bioavailability of omecamtiv mecarbil was high (> 75%) for 3 of the five MR formulations. Food had a marginal, nonclinically meaningful effect on the pharmacokinetics of the MR formulations of omecamtiv mecarbil.
    No preview · Article · Dec 2015 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Objective: Cardiovascular disease (CVD) is one of the major burdens on societies and healthcare systems. Antiplatelet aspirin is used to prevent the occurrence or reoccurrence of cardiovascular events. However, studies have shown that a good portion of patients still suffer from cardiovascular events in spite of using aspirin (also called aspirin nonresponders). On the other hand, angiotensin-converting enzyme inhibitors (ACEIs) as well as angiotensin-receptor blockers (ARBs) are widely used in patients with different spectrums of cardiovascular diseases. In this study, the possible interactive effect of ACEIs and ARBs on aspirin response was evaluated in vitro. Methods: A multiplate analyzer was used to assay the possible interactions between ACEIs and ARBs drugs on antiplatelet effect of aspirin using blood obtained from 6 healthy volunteers. Means of area under the aggregation curves (AUCs) of the blood samples treated with 10 μg/mL aspirin were calculated before and after exposure to captopril, lisinopril, candesartan, or losartan. Results: Results showed potential antithrombotic effect of ACEIs and ARBs only at high concentrations (3.3 μg/mL).The antiplatelet effect of aspirin 10 μg/mL was significantly enhanced by the addition of captopril or lisinopril at high dose (3.3 μg/mL), candesartan at all tested doses (0.03 μg/mL, 0.33 μg/mL, 3.3 μg/mL), and losartan at doses of 0.33 μg/mL and 3.3 μg/m. Conclusion: Treatment with ACEIs (captopril and lisinopril) and ARBs (candesartan and losartan) improved the antiplatelet response to aspirin. Further studies are needed to confirm this action and potentially apply it to clinical practice.
    No preview · Article · Dec 2015 · International journal of clinical pharmacology and therapeutics
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    ABSTRACT: Hemocoagulase agkistrodon for injection is the national first-class new drug of China with good hemostatic function and safety for capillary hemorrhage in abdominal incision of surgical patients. Adverse drug reactions (ADRs) to hemocoagulase agkistrodon are rarely reported. In this paper, we describe a case of a 41-year-old woman who developed anaphylactic shock attributed to hemocoagulase agkistrodon before colon cancer surgery. Based on the Naranjo ADR probability score, a "probable" cause and effect relationship existed for this case. Although the cause of anaphylactic reaction (hemocoagulase or excipient) and exact mechanism of hemocoagulase agkistrodon-induced anaphylactic reaction are unknown, attention should be drawn to potential ADRs in clinical use.
    No preview · Article · Dec 2015 · International journal of clinical pharmacology and therapeutics