W M Awni

Cairo University, Al Qāhirah, Al Qāhirah, Egypt

Are you W M Awni?

Claim your profile

Publications (91)374.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: ABT-639 is a selective T-type calcium channel blocker with efficacy in a wide range of preclinical models of nociceptive and neuropathic pain. In the current first-in-human (FIH) study, the pharmacokinetics, tolerability, and safety of ABT-639 after single- (up to 170 mg) and multiple doses (up to 160 mg BID) were evaluated in healthy volunteers in a randomized, double-blinded, placebo-controlled manner. ABT-639 demonstrated acceptable safety and pharmacokinetic profiles in human. Results from assessment of the routine laboratory variables showed an unexpected statistically significant and clinically relevant decrease in blood uric acid with the increase in ABT-639 dose, which is possibly due to inhibition in URAT1 transporter. Pharmacokinetic/pharmacodynamic models were constructed to characterize the relationship between ABT-639 exposure and uric acid response. The final model was a mechanism-based indirect response pharmacodynamic model with the stimulation of uric acid elimination by ABT-639. The model estimated K in values in males and females were 10.2 and 7.13 μmol/h, respectively. The model estimated K out was 0.033 1/h. ABT-639 concentration that can produce 50% stimulation in uric acid elimination was estimated to be 8,070 ng/mL. Based on the final model, further simulations were conducted to predict the effect of ABT-639 on uric acid in gout patients. The simulation results indicated that, if the urate-lowering response to ABT-639 in gout patients is similar to that in healthy subjects, ABT-639 BID doses of 140 mg or higher would be expected to provide clinically meaningful lowering of blood uric acid levels below the 380 μmol/L solubility limit of monosodium urate.
    The AAPS Journal 01/2015; · 3.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lortab® Elixir, a proprietary combination product containing hydrocodone and acetaminophen, is approved in the U.S. for the treatment of moderate to moderately severe pain in children. Despite this approval, pediatric pharmacokinetic data using this product have not been previously published. Using a single-dose open-label study approach, we evaluated the pharmacokinetics, tolerability and safety of this product in 17 healthy children 6 to 17 years of age. Results showed that the body weight-normalized oral clearance (L/hr/kg) of hydrocodone and acetaminophen were 42% and 27% higher, respectively when compared to data from healthy adults. This suggests thathigher mg/kg dose, but not the absolute dose, would be required in children to achieve exposures similar to adults. We found adjustment of hydrocodone and acetaminophen dose by body surface area to be more optimal than body weight based dose adjustment for achieving similar systemic exposure in children and adults. However, body weight-based hydrocodone and acetaminophen dosing regimen provided close approximation of adult exposuresin pediatric patients with approximately 22% to 24% lower hydrocodone and acetaminophen dose/BW-normalized AUC in pediatric patients compared to adults. Finally, the adverse event profile in our pediatric cohort was consistent with that expected of opioid-naive subjects receiving opioid-combination therapy.
    The Journal of Clinical Pharmacology 09/2014; · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Navitoclax is a first-in-class, orally bioavailable, targeted Bcl-2 family protein inhibitor and promotes apoptosis. Thrombocytopenia is a primary dose-limiting toxicity of navitoclax which exhibited a distinct time profile in circulating platelets from that caused by traditional chemotherapies. A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the pharmacokinetic of navitoclax as well as the time course of the platelet counts in cancer patients receiving navitoclax.
    Cancer Chemotherapy and Pharmacology 07/2014; · 2.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Biopharmaceutical studies for anti-cancer drugs are typically conducted in cancer patients due to unacceptable toxicities to healthy volunteers. Navitoclax is a first-in-class, orally bioavailable, targeted Bcl-2 family protein inhibitor that has been studied in cancer patients. Methods: A strategy that integrated the evaluation of non-clinical toxicology data and clinical data in cancer patients was employed to assess the feasibility, determine doses and establish risk management plans for studying navitoclax in healthy volunteers. Two relative bioavailability/food effect studies with either a 25 mg dose or 50 and 100 mg doses of navitoclax were conducted sequentially in healthy female volunteers of non-childbearing potential. Results/Conclusion: Navitoclax was well-tolerated in both studies in healthy volunteers, and did not impose risks beyond the minimal levels expected in healthy volunteer studies. Compared to a similar study in cancer patients, the studies in healthy volunteers generated higher quality data in a short period of time to support formulation selection.
    Anticancer research 07/2014; 34(7):3739-46. · 1.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABT-384 is a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (HSD-1). ABT-384 pharmacokinetics was evaluated in healthy volunteers in single-dose (1, 8, 20, 50, 120 and 240 mg) and multiple-dose studies (1, 2, 4, 8, 20, 30 and 100 mg). Less than dose-proportional pharmacokinetics of ABT-384 was observed when ABT-384 was administered at single doses lower than 8 mg. This nonlinear phenomenon disappeared after repeated doses. The dose-normalized plasma concentration-time curves superposed across all dose groups on Day 7, but not on Day 1. This phenomenon cannot be explained by the half-life of ABT-384. Based on available data, the nonlinearity is likely due to binding of ABT-384 to a high-affinity-low-capacity site, such that this interaction was reflected in ABT-384 pharmacokinetics. To characterize pharmacokinetics of ABT-384, a population pharmacokinetic model for ABT-384 was constructed. The model provided reasonable fitting for both single- and multiple-dose data. Further investigation is warranted to evaluate the disposition of ABT-384 at low doses using a larger number of subjects. The constructed model would be useful in predicting ABT-384 concentrations at different doses and guiding selection of dosing regimens in further clinical trials. This article is protected by copyright. All rights reserved.
    Biopharmaceutics & Drug Disposition 07/2014; · 2.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Linifanib is a selective inhibitor of the vascular endothelial growth factor and platelet-derived growth factor family of tyrosine kinase inhibitors. The purpose of this high-precision QT study was to evaluate the effects of linifanib on cardiac repolarization in patients with advanced metastatic tumors. Enrolled patients (n = 24) had measurable disease refractory to standard therapies, ECOG performance status of 0-1, and adequate organ function. Patients were randomized in a 2-sequence, 2-period crossover design. Serial ECG measurements and pharmacokinetic samples were collected for each crossover period. An intersection-union test was performed for time-matched baseline-adjusted QTcF intervals. An exposure-response analysis was explored to correlate the plasma concentration and QTcF. The maximum 95 % upper confidence bound for the baseline-adjusted QTcF was 4.3 ms at hour 3 at the maximum tolerated linifanib dose of 0.25 mg/kg. Linifanib did not meet the regulatory threshold (10 ms) for QT prolongation. Exposure-response modeling showed that the QTcF change was not significant at the maximum plasma concentration. Linifanib does not significantly affect cardiac repolarization in patients with advanced solid tumors.
    Cancer Chemotherapy and Pharmacology 11/2013; · 2.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABT-384 is a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (HSD-1), the enzyme that regenerates cortisol in several tissues. Two clinical studies of ABT-384 were undertaken to assess its safety, pharmacokinetics, target engagement, and pharmacologic effects in healthy subjects. Single doses from 1 to 240 mg, and multiple doses from 1 to 100 mg once daily for 7–14 days, were administered to healthy adults. Multiple doses from 10 to 100 mg once daily for 21 days were administered to elderly subjects. A total of 103 subjects received at least 1 dose of ABT-384. A maximum-tolerated dose was not defined in either study. The pharmacokinetic profiles of ABT-384 and its active metabolite support once daily dosing. Analysis of urine cortisol metabolites demonstrated full hepatic HSD-1 inhibition with regimens from 1 mg daily, and confirmed in vitro target selectivity. Pharmacologic effects included increases of adrenocorticotrophic hormone levels, cortisol production and androgen and estradiol levels. ABT-384 has a wide therapeutic index relative to full hepatic target engagement which is relevant for indications such as diabetes and metabolic syndrome. Its therapeutic index for other potential indications such as Alzheimer's disease remains to be established.
    Clinical Pharmacology in Drug Development. 04/2013; 2(2).
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABT-384 is a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (HSD-1). ABT-384 has been shown to be safe and well tolerated in man at doses up to 100 mg QD, and to fully inhibit both peripheral and brain HSD-1 at a dose of 2 mg QD. The effect of ketoconazole on the pharmacokinetics of ABT-384 and its two active metabolites A-1331480 and A-847082 was investigated in healthy volunteers. When 10 mg of ABT-384 was co-administered with ketoconazole, ABT-384 exposures increased 18-fold for AUC∞ and 3.5-fold for C(max). The results suggest that ABT-384 is a sensitive substrate of CYP3A. After ketoconazole co-administration, exposures of A-1331480 and A-847082 were also greatly increased. A population pharmacokinetic modeling was constructed for ABT-384 and its metabolites using NonMEM. A 2-compartment model with 3 transit absorption compartments best described ABT-384 data. The model predicted a 69.3% decrease in ABT-384 clearance and 91.1% increase in the volume of distribution of ABT-384 in the presence of ketoconazole. A-1331480 was shown to be formation rate-limited and A-847082 was elimination rate-limited. Both metabolites were characterized by 1-compartment model with first-order rate constants of formation and elimination. Overall the model adequately captured the concentration-time profiles of ABT-384, A-1331480 and A-847082 in both ABT-384 alone and ketoconazole co-administration conditions. Although ABT-384 exposures were greatly increased in the presence of ketoconazole, co-administration of ABT-384 with ketoconazole or other strong/moderate CYP3A inhibitors is not expected to contribute to any major clinical safety issues considering the favorable safety profile of ABT-384.
    Drug metabolism and disposition: the biological fate of chemicals 02/2013; · 3.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIM: To quantitatively characterize the relationship between ABT-102, a potent and selective TRPV1 antagonist, exposure and its effects on body temperature in humans using a population pharmacokinetic/pharmacodynamic modeling approach. METHODS: Serial pharmacokinetic and body temperature (oral or core) measurements from 3 double-blind, randomized, placebo-controlled studies [single-dose (2, 6, 18, 30 and 40 mg; solution formulation), multiple-dose (2, 4, and 8 mg BID for 7 days; solution formulation) and multiple-dose (1, 2, and 4 mg BID for 7 days; solid-dispersion formulation)] were analyzed. NONMEM was used for model development and the model building steps were guided by pre-specified diagnostic and statistical criteria. The final model was qualified using non-parametric bootstrap and visual predictive check. RESULTS: The developed body temperature model included additive components of baseline, circadian rhythm (cosine function of time) and ABT-102 effect (E (max) function of plasma concentration) with tolerance development (decrease in ABT-102 E (max) over time). Type of body temperature measurement (oral vs. core) was included as a fixed effect on baseline, amplitude of circadian rhythm, and residual error. The model estimates (95% bootstrap confidence interval) were: baseline oral body temperature, 36.3 (36.3-36.4)°C; baseline core body temperature, 37.0 (37.0-37.1)°C; oral circadian amplitude, 0.25 (0.22-0.28)°C; core circadian amplitude, 0.31 (0.28-0.34)°C; circadian phase shift, 7.6 (7.3-7.9) hr; ABT-102 E(max), 2.2 (1.9-2.7)°C; ABT-102 EC (50), 20 (15-28) ng/mL; tolerance T (50), 28 (20-43) hr. CONCLUSIONS: At exposures predicted to exert analgesic activity in humans, ABT-102 effect on body temperature is estimated to be 0.6 to 0.8 °C. This effect attenuates within 2 to 3 days of dosing.
    British Journal of Clinical Pharmacology 08/2012; · 3.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABT-594, a neuronal nicotinic acetylcholine receptor ligand, is 30- to 100-fold more potent than morphine in animal models of nociceptive and neuropathic pain. Efficacy and safety of ABT-594 in subjects with painful diabetic polyneuropathy was evaluated in a phase 2 study. The objective of this work was to use a nonlinear mixed effects model-based approach for characterizing the relationship between dose and response (efficacy and safety) of ABT-594. Subjects (N = 266) were randomized into four groups in a double-blind, placebo-controlled, 7-week study to receive twice daily regimens of placebo or 150, 225, and 300 μg of ABT-594. The primary efficacy variable, pain score (11-point Likert scale), was assessed on five occasions. The probability of change from baseline pain score of ≥1, ≥2, and ≥3 was modeled using cumulative logistic regression with dose and days of treatment as explanatory variables. The incidence of five most frequently occurring adverse events (AEs) was modeled using linear logistic regression. ABT-594 ED(50) values (improvement in 50% of subjects) for improvement in pain scores of ≥1, ≥2, and ≥3 were 50, 215, and 340 μg, respectively, for the average number of days (33) on treatment. The rank order of ED(50) values for AEs was nausea, vomiting, dizziness, headache, and abnormal dreams; nicotine users were less sensitive to AEs. Population pharmacodynamic models developed to characterize the improvement in pain score and incidence of adverse events indicate an approximately twofold separation between the ED(50) values for efficacy and AEs.
    The AAPS Journal 02/2012; 14(2):168-75. · 3.91 Impact Factor
  • S Dutta, W Awni
    [Show abstract] [Hide abstract]
    ABSTRACT: ABT-594 is a non-opioid, non-NSAID analgesic. The objective of this work was to characterize the population pharmacokinetics of ABT-594 in subjects with neuropathic pain. Efficacy, safety and pharmacokinetics of ABT-594 in subjects with painful diabetic polyneuropathy were evaluated in a randomized, double-blind, placebo-controlled, parallel-group, multi-centre, 7-week Phase 2 study. Subjects (N=266) were approximately equally divided into four groups to receive BID regimens of placebo or 150, 225 and 300 μg of ABT-594. ABT-594 concentrations were determined from all subjects, whereas a subset of subjects provided intensive pharmacokinetic samples on two occasions. One- and two-compartment models were explored for characterizing plasma ABT-594 concentration-time profiles. The relative importance of covariates (age, weight, body surface area, creatinine clearance, gender, nicotine use and albumin concentrations) was examined by use of the likelihood ratio test. Model building was accomplished using stepwise forward selection (P<0·05) and backward elimination (P<0·005) of covariates. Population analyses were performed using NONMEM. Optimal characterization of the plasma concentration data was achieved using a one-compartment base model. Creatinine clearance and age were found to be significant covariates in the forward selection process; backward elimination process identified only creatinine clearance as a significant covariate. A population pharmacokinetic model was developed to characterize ABT-594 concentrations in subjects with neuropathic pain. As ABT-594 is primarily eliminated as unchanged drug in the urine, creatinine clearance and age were significant covariates of clearance with creatinine clearance being the optimal predictor of ABT-594 clearance.
    Journal of Clinical Pharmacy and Therapeutics 12/2011; 37(4):475-80. · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Paricalcitol injection and capsules are approved for the prevention and treatment of secondary hyperparathyroidism. Exposure-response analyses were performed to describe paricalcitol pharmacokinetics and the relationship to clinical responses (intact parathyroid hormone [iPTH], serum calcium, and phosphorus) following administration of paricalcitol capsules or injection to patients with chronic kidney disease (stage 5). Paricalcitol pharmacokinetics were similar following intravenous and oral administration with mean oral clearance of 1.75 L/h and bioavailability of 75.1%. Exposure-clinical response was best described by an indirect effects model where serum iPTH, calcium, and phosphorus production rates were directly affected by paricalcitol. Significant covariates in the response model included screening iPTH, calcium, and phosphorus on their corresponding synthesis rates; age on iPTH EC(50); and bone-specific alkaline phosphatase on calcium EC(50) (CRIT). This exposure-response model was used in extensive clinical trial simulations to assess alternative dose regimens for CKD stage 5 patients.
    The Journal of Clinical Pharmacology 09/2011; 52(8):1162-73. · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A study was conducted in healthy adults (n = 19) to evaluate the pharmacokinetics of lopinavir/ritonavir when coadministered with efavirenz. Participants were administered lopinavir/ritonavir 400/100 mg alone twice daily (bid) from the morning of day 1 through the morning of day 10, and then lopinavir/ritonavir 500/125 mg bid was coadministered with efavirenz 600 mg every evening (qhs) from the evening of day 10 through day 20. Lopinavir and ritonavir exposures when administered alone versus with efavirenz were determined on days 10 and 20 and compared using point estimates and 90% confidence intervals. The point estimates for the ratios of lopinavir maximum observed plasma concentration (C(max)), plasma concentration prior to morning dosing (C(trough)), and area under the plasma concentration-time curve over a dosing interval (AUC(12)) were 1.121, 0.954, and 1.060, respectively. The lopinavir/ritonavir dose of 500/125 mg bid administered with efavirenz most closely approximates the pharmacokinetic exposure of lopinavir/ritonavir 400/100 mg bid administered alone.
    The Journal of Clinical Pharmacology 06/2011; 52(8):1248-54. · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABT-102 is a selective TRPV1 antagonist with robust efficacy in several preclinical models of pain. Three phase 1 studies evaluated ABT-102 pharmacokinetics upon oral administration to healthy human volunteers: a single-dose study (2, 6, 18, 30, and 40 mg) and a multiple-dose study (2, 4, and 8 mg twice daily for 7 days) using a solution formulation and a multiple-dose study (1, 2, and 4 mg twice daily for 7 days) using a solid-dispersion formulation. These studies followed double-blind, randomized, placebo-controlled designs. ABT-102 exhibited dose- and time-linear pharmacokinetics. ABT-102 half-life ranged from 7 to 11 hours, and steady state was achieved by day 5 of dosing. Population analysis of the pharmacokinetic data from the 3 studies was conducted. A 1-compartment model with a transit compartment for absorption and first-order elimination provided best fit to the data. The model included formulation-dependent lag times and a bioavailability factor (F(rel)) for solution relative to solid dispersion. The population parameter estimates (95% bootstrap confidence intervals) were oral clearance, 16 (14-18) L/h; oral volume of distribution, 215 (192-237) L; transit rate constant, 1.4 (1.3-1.6) h(-1); solid-dispersion lag, 0.6 (0.5-0.8) h; solution lag, 0.3 (0.2-0.4) h; and solution F(rel), 40% (35%-45%). Evaluation of ABT-102 pharmacokinetic model indicated its robustness and adequacy.
    The Journal of Clinical Pharmacology 06/2011; 52(7):1028-41. · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABT-107 is a potent, selective α7 nicotinic receptor agonist under development for treatment of Alzheimer's disease and cognitive deficits associated with schizophrenia. The pharmacokinetics, safety, and tolerability of escalating single oral doses (1, 3, 10, 30, 60, 80, and 100 mg; double-blind, placebo-controlled, randomized, incomplete crossover design) and multiple oral doses (2, 6, and 15 mg once daily for 7 days; double-blind, placebo-controlled, randomized, parallel-group design) of ABT-107 were evaluated. Additionally, effect of food on ABT-107 pharmacokinetics (20-mg single dose) was evaluated using an open-label, 2-period, fasting and nonfasting, randomized, complete crossover design. ABT-107 exhibited nonlinear (more than dose-proportional) pharmacokinetics. ABT-107 half-life ranged from 7 to 10 hours, and steady state was achieved by day 6 of dosing. Food did not have a clinically meaningful effect on ABT-107 exposure. ABT-107 was safe and well tolerated over the tested dose range. The most frequently reported adverse events were nausea, headache, and tremor following single dosing and somnolence following multiple dosing. The pharmacokinetics, safety, and tolerability profiles of ABT-107 pose it as a good candidate for further development.
    The Journal of Clinical Pharmacology 04/2011; 51(4):512-26. · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABT-335 is the choline salt of fenofibric acid under clinical development as a combination therapy with rosuvastatin for the management of dyslipidemia. ABT-335 and rosuvastatin have different mechanisms of actions and exert complementary pharmacodynamic effects on lipids. The current study assessed the pharmacokinetic interaction between the 2 drugs following a multiple-dose, open-label, 3-period, randomized, crossover design. Eighteen healthy men and women received 40 mg rosuvastatin alone, 135 mg ABT-335 alone, and the 2 drugs in combination once daily for 10 days. Blood samples were collected prior to dosing on multiple days and up to 120 hours after day 10 dosing for the measurements of fenofibric acid and rosuvastatin plasma concentrations. Coadministering 40 mg rosuvastatin had no significant effect on the steady-state Cmax, Cmin, or AUC24 of fenofibric acid (P > .05). Coadministering ABT-335 had no significant effect on the steady-state Cmin or AUC24 of rosuvastatin (P > .05) but increased Cmax by 20% (90% confidence interval: 12%-28%). All 3 regimens were generally well tolerated with no clinically significant changes in clinical laboratory values, vital signs, or electrocardiograms during the study. Results from this study demonstrate no clinically significant pharmacokinetic interaction between ABT-335 at the full clinical dose and rosuvastatin at the highest approved dose.
    The Journal of Clinical Pharmacology 10/2008; 49(1):63-71. · 2.47 Impact Factor
  • Journal of Cardiac Failure 08/2007; 13(6). · 3.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lopinavir, an HIV protease inhibitor, is coformulated with ritonavir to enhance the bioavailability and pharmacokinetics of lopinavir. The original solid oral formulation of lopinavir/ritonavir, a soft-gelatin capsule (SGC), requires refrigerated storage, is taken as 6 capsules daily at the recommended adult dose, and is administered with food to maximize the bioavailability of lopinavir. Melt extrusion technology was used to produce a tablet formulation reducing the number of dosage units administered per day and simplifying storage requirements. Three studies assessed the bioavailability of tablet doses of lopinavir/ritonavir at 800/200 mg or 400/100 mg under different meal conditions compared with equal doses of the SGC after a moderate-fat meal. The tablet was bioequivalent to the SGC after a moderate-fat meal with respect to lopinavir and ritonavir areas under the concentration-time curve. Compared with the SGC formulation, the tablet formulation resulted in more consistent lopinavir and ritonavir exposures within and across studies and across meal conditions. The diminished food effect and decreased variability of the tablet are likely to result in more consistent lopinavir and ritonavir exposures, minimizing the likelihood of extreme high or low values compared with the SGC.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2007; 44(4):401-10. · 4.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have shown that coadministration of certain protease inhibitors (PIs) with gastric acid-reducing agents results in decreased plasma concentrations of the PI. To assess the effect of acid-reducing agents on lopinavir/ritonavir, data from two clinical trials (n = 38 and 190) were pooled. Both trials randomized antiretroviral-naïve, HIV-infected patients to receive lopinavir/ritonavir 400/100 mg twice-daily or 800/200 mg once-daily in combination with stavudine and lamivudine, or tenofovir and emtricitabine. Concurrent administration of gastric acid-reducing agents including antacids of various brand names, proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole), and H(2)-receptor antagonists (ranitidine, famotidine, cimetidine, and nizatidine) was reported in both trials. Lopinavir and ritonavir pharmacokinetic parameters were evaluated. Thirty subjects were considered users of acid-reducing agents at the times of pharmacokinetic evaluation. HIV-infected patients who received gastric acid-reducing agents during administration of lopinavir/ritonavir-based treatment regimens did not appear to have a reduction in lopinavir or ritonavir exposures.
    AIDS PATIENT CARE and STDs 05/2007; 21(4):247-51. · 3.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Paricalcitol capsules are indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease (CKD). Proton pump inhibitors are prescribed to CKD patients to treat gastroesophageal reflux. This was a single dose, crossover study evaluating the effect of omeprazole, change in gastric pH as a result thereof, on the pharmacokinetics (PK) of paricalcitol. Twenty-six healthy subjects were administered paricalcitol capsules (16 microg) alone (regimen A), and following a single dose of OMP (40 mg) (regimen B), with a washout of at least 7 days. Plasma samples for paricalcitol concentrations were collected for 48 h post-paricalcitol dose. The plasma paricalcitol concentrations were measured using an LC-MS/MS assay (LOQ=0.02 ng/ml) and paricalcitol pharmacokinetic parameters were estimated using non-compartmental methods. The point estimates and the corresponding 90% confidence intervals for Cmax and AUC0-infinity to evaluate paricalcitol-omeprazole interaction were 1.032 [0.920-1.158] and 1.041 [0.951-1.139], respectively. No significant differences in Tmax (regimen A: 2.9 h vs regimen B: 2.6 h) or t1/2 (6.83 h vs 6.6 h) between the regimens were observed. Hence, the co-administration of omeprazole does not affect the PK of paricalcitol. Both regimens were well tolerated and no apparent differences among the regimens with respect to safety were observed.
    Biopharmaceutics & Drug Disposition 04/2007; 28(2):65-71. · 2.18 Impact Factor

Publication Stats

1k Citations
374.48 Total Impact Points


  • 2012
    • Cairo University
      Al Qāhirah, Al Qāhirah, Egypt
  • 1995–2012
    • Abbott Laboratories
      • Abbott Laboratories
      North Chicago, Illinois, United States
  • 1988–1993
    • University of Minnesota Duluth
      • College of Pharmacy
      Duluth, Minnesota, United States
  • 1987–1993
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States