C H Nightingale

Hartford Hospital, Hartford, Connecticut, United States

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Publications (172)606.57 Total impact

  • Source
    D P Niclau · p R Tessier · I Rubinstein · C H Nightingale ·
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    ABSTRACT: In addition to bactericidal activity, macrolide antibacterials possess clinically relevant properties such as immunomodulatory activity. Whether such activity extends to novel antibacterials that are structurally related to macrolides, such as the ketolides, remains largely unknown. The objective of this study was to evaluate the in vivo immunomodulatory profile of the first ketolide antibacterial - telithromycin in a murine neutropenic thigh infection model. Specific pathogen-free, female ICR mice were rendered transiently neutropenic with intraperitoneal cyclophosphamide. Thighs were inoculated with 10(6) colony-forming units of a single clinical isolate of Streptococcus pneumoniae. Once inoculated, mice (n=500) received single oral doses of telithromycin (10, 25 or 50 mg/kg of body weight) or no treatment (control). Blood was obtained via cardiac puncture prior to and at 2, 4, 8, and 24 h after dose administration for determination of cytokine concentrations. Significant post-inoculation elevations of interleukin (IL)-1beta, IL-6, and IL-10 were noted in untreated controls over 24 h. Telithromycin attenuated these increases and the suppression of both IL-6 and IL-10 release was observed to be dose dependent. Systemic concentrations of IL-2 and tumor necrosis factor alpha showed an upward trend over the initial 8-h post-inoculation period in the telithromycin group. These data therefore reveal novel in vivo immunomodulatory effects of telithromycin. Further studies are warranted to determine whether such effects contribute to the therapeutic efficacy of the drug in patients with acute respiratory tract infections.
    Pharmazie 05/2006; 61(4):343-7. · 1.05 Impact Factor
  • C.T. Ong · P.K. Dandekar · C Sutherland · C.H. Nightingale · D.P. Nicolau ·
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    ABSTRACT: Antimicrobial efficacy is dependent on the ability of the agent to reach the site of infection. To assess the bronchopulmonary drug disposition of a novel ketolide, telithromycin (TEL), the epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations were utilized as a surrogate marker for lung penetration. Adult subjects scheduled for diagnostic bronchoscopy received oral TEL 800 mg once daily for 5 days. Plasma and bronchoalveolar lavage (BAL) samples were collected 2, 8, 12, or 24 h after the last TEL dose. TEL concentrations in the ELF and AM were determined using a validated HPLC assay. ELF drug concentrations were calculated using the urea dilution method. Seventeen subjects with a mean age 65 +/- 13 years and a mean weight of 81 +/- 25 kg completed this open-label study. The median (range) TEL concentrations in plasma and ELF, respectively, were 1.09 mg/l (1.00-4.81) and 3.91 mg/l (2.64-9.59) at 2 h (n = 6), 0.48 and 1.09 mg/l at 8 h (n = 1), 0.65 mg/l (0.18-1.55) and 1.81 mg/l (0.61-10.0) at 12 h (n = 5), and 0.11 mg/l (0.09-0.24) and 0.69 mg/l (0.15-1.58) at 24 h (n = 5). The median AM concentrations obtained from these subjects were 53.35 mg/l at 2 h, 32.55 mg/l at 8 h, 65.96 mg/l at 12 h, and 26.43 mg/l at 24 h. Overall TEL was well tolerated. No discontinuation was required due to an adverse event. TEL displayed high intrapulmonary penetration with ELF concentrations exceeding that of plasma at all time points. AM intracellular concentrations were multiple times higher than in the ELF and plasma. These data support the clinical efficacy of TEL against intracellular and extracellular pathogens, particularly with Streptococcus pneumoniae having an MIC(90 )well below achievable concentrations at the site of infection.
    Chemotherapy 11/2005; 51(6):339-46. DOI:10.1159/000088958 · 1.29 Impact Factor
  • C H Nightingale ·
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    ABSTRACT: Objective: This study evaluated the quality of 40 generic clarithromycin products from Latin America and Asia. Materials and Methods: The generic products were examined visually, assayed by high pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories. Results: This survey found that many generic clarithromycin products are not equivalent to the innovator product, falling short of the approved, registered specifications for the innovator product. Overall, 20% (8 of 40) of all generic tablets tested, and 33% (6 of 18) of tablets from Latin America, failed to contain between 95 and 105% of the clarithromycin claimed in the label, thus falling short of the approved registered specification for the innovator product. A total of 70% (28 of 40) of products tested released less drug in 30 minutes than did the innovator tablets, although they still met the dissolution specification requiring that 80% of the drug must dissolve in 30 minutes; one generic product failed to meet the specification. A total of 60% (24 of 40) of the generic products tested exceeded the Abbott Laboratories' 3% limit for total impurities in bulk drug, and 70% (28 of 30) exceeded the Abbott Laboratories' 0.8% limit for 6,11 di-O-methyl erythromycin A. Conclusions: These results suggest that generic tablets are not equivalent to the innovator product, raising concerns that clinical trial results achieved with branded clarithromycin (Abbott Laboratories) should not be extrapolated to generic products.
    Clinical Drug Investigation 02/2005; 25(2):135-52. DOI:10.2165/00044011-200525020-00006 · 1.56 Impact Factor
  • N R Florea · B Capitano · C H Nightingale · D Hull · G J Leitz · D P Nicolau ·
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    ABSTRACT: Itraconazole is often given for fungal prophylaxis to renal transplant recipients, who require concomitant cyclosporine in the immediate posttransplant period. We determined the extent of the pharmacokinetic interaction between cyclosporine and itraconazole oral solution in renal transplant recipients and the effect on daily drug costs. This was a single-center, open-label, nonrandomized study. Posttransplantation, renal transplant recipients received itraconazole solution 200 mg twice daily and cyclosporine, dosed to achieve target concentrations. Once at steady state, blood samples were collected over 12 hours for pharmacokinetic evaluation of cyclosporine, itraconazole, and hydroxy-itraconazole. Itraconazole was discontinued after approximately a 3-month prophylaxis regimen. Cyclosporine doses were titrated to achieve target concentrations and cyclosporine concentrations were once again determined when steady state was achieved. A noncompartmental analysis was used to analyze cyclosporine pharmacokinetic parameters. The pharmacoeconomic impact was measured based on the percent change in dose of cyclosporine when administered with and without itraconazole. Drug costs were calculated using the average wholesale price. The cost per patient, as well as the average cost, was calculated for the cyclosporine/itraconazole combination, as well as the cyclosporine regimen alone. Eight renal transplant recipients completed the study. All were included for itraconazole analyses and seven for cyclosporine analyses. Mean peak and trough itraconazole levels were 1.64 +/- 0.82 and 1.23 +/- 0.90 microg/mL respectively. Mean peak and trough hydroxy-itraconazole levels were 2.37 +/- 1.55 and 2.20 +/- 1.48 microg/mL, respectively. While on itraconazole, a 48% reduction in the mean total daily dose of cyclosporine was necessary to maintain target concentrations (171 +/- 63.6 versus 329 +/- 103.5 mg, P =.003). This reduction in cyclosporine dose resulted in a discounted itraconazole daily drug cost of approximately 29.5%. Administering itraconazole with cyclosporine allows for a decrease in the cyclosporine dose, thus lowering daily drug costs and providing adequate antifungal coverage with itraconazole and hydroxy-itraconazole trough concentrations above the MIC(90) of Candida and Aspergillus spp.
    Transplantation Proceedings 01/2004; 35(8):2873-7. DOI:10.1016/j.transproceed.2003.10.058 · 0.98 Impact Factor
  • M K Kim · M A Banevicius · M Zhong · X Shi · M Hu · C H Nightingale · D P Nicolau ·
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    ABSTRACT: Quinupristin-dalfopristin (Q/D) is often utilized in critically ill patients, some of whom require CVVH. This study was undertaken to determine the clearance of O/D and their main active metabolites (RPR 100391, RP 69012, RP 12536) via CVVH in the swine model. Q/D 7.5 mg/kg was intravenously administered over 0.5 h to 12 swine after induction of acute renal failure by ligation of the renal arteries. At 0.5 h post injection, the CVVH procedure was initiated and continued for 8 hours at the following pump rates: (1)100 mL/min, (2)180 rnL/min, and (3)100 mL/min with dialysis (flow rate: 1 L/h). Blood and ultrafiltrate samples were collected at 1 h intervals and assessed by a validated HPLC method. Plasma analysis suggests rapid metabolism to the main active metabolites which are appreciably cleared as demonstrated by high clearance and sieving coefficient estimates. Mean clearance estimates for RP 69012, RP 100391, and RP 12536 are 729, 777, and 578 mL/h in the 100 mL/min CVVH group, 772, 785, 685 mL/min in the 180 mL/min CVVH group, and 753, 791, 616 mL/min in the 100 mL/min CVVH group with 1 L/h dialysis, respectively. These data reveal that Q/D is rapidly metabolized and the metabolites are cleared to a large extent via CVVH. Due to the considerable contribution of the metabolites to overall in vivo activities, additional studies are required to fully quantify their removal before final dosage modifications for patients undergoing CVVH can be recommended.
    The International journal of artificial organs 02/2002; 25(1):33-9. · 0.96 Impact Factor
  • M K Kim · D Xuan · R Quintiliani · C H Nightingale · D P Nicolau ·
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    ABSTRACT: A multiple-dose, open-labelled, randomized, two period crossover human volunteer study was performed (i) to describe the pharmacokinetic profile and safety profile of piperacillin and tazobactam (P/T) administered 6.0/0.75 g and 8.0/1.0 g q12h and (ii) to characterize the pharmacodynamic profile of these regimens against a variety of common targeted pathogens. Blood samples were collected after the third dose and concentrations of P/T were determined by a validated high-performance liquid chromatography assay. Pharmacokinetic profiles of P/T were determined by non-compartment analysis. Percentage time above the MIC (%T > MIC) of piperacillin was calculated for a range of MICs. In this study, no adverse events were attributed after multiple administrations of either 6.0/0.75 g or 8.0/1.0 g dose regimens. The peak concentration, half-life and area under the curve (AUC0-(0-tau)) of piperacillin were significantly different by a paired t-test (P < 0.05) between the two study regimens. The trough concentration, half-life and area under the curve (AUC0-(0-tau)) of tazobactam were substantially different from parameters reported previously for conventional regimens. The 8.0/1.0 g regimen provided 50% T > MIC for MICs < or =32 mg/L, while a similar value for the 6.0/0.75 g regimen was < or = 16 mg/L. High-dose P/T regimens with extended interval were well tolerated and provide adequate dynamic exposure for a variety of susceptible pathogens.
    Journal of Antimicrobial Chemotherapy 09/2001; 48(2):259-67. · 5.31 Impact Factor
  • W. Zhou · C.H. Nightingale · G.A. Davis · D.P. Nicolau ·
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    ABSTRACT: The study was undertaken to evaluate the single-dose absorption, elimination, and systemic bioavailability of enterally administered fluconazole relative to intravenous fluconazole in ICU patients. Fluconazole pharmacokinetics were evaluated in five patients who had normal gastrointestinal motility, normal renal and hepatic function. A single 200 mg dose of fluconazole was administered either as an intravenous infusion over 1 h or the suspension given via a feeding tube in a crossover design. Fluconazole serum concentrations were determined by a validated HPLC method and the pharmacokinetic parameters of fluconazole were calculated using non-compartmental analysis. The absolute bioavailability of the suspension as determined by a ratio AUC susp/AUC IV was 77.4±44%.
    Journal of Infectious Disease Pharmacotherapy 01/2001; 5(1):27-35.
  • D Xuan · J F Lu · D P Nicolau · C H Nightingale ·
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    ABSTRACT: The population pharmacokinetics of tobramycin was investigated in a group of 327 adult hospitalized patients receiving once-daily administration of tobramycin at a dose of 7 mg kg(-1). The patients had an average age of 57+/-18 y and an average weight of 65+/-14 kg; 153 of the patients were female. Data, comprised of 575 serum concentrations, were analyzed using a nonlinear mixed-effect model (NONMEM) with a first-order conditional estimation method and were best described with a one-compartment model. The patient covariates including body weight, gender, age and creatinine clearance (CL(CR)) were added in a stepwise fashion to identify their potential influences on tobramycin pharmacokinetics. Results showed that tobramycin clearance (CL) was linearly correlated with CL(CR) (proportionality constant: 0.066+/-0.002 x CL(CR) (ml min(-1))) and the volume of distribution (Vd) was linearly related to body weight (proportionality constant: 0.40+/-0.024 x body weight (1 kg(-1))). The mean population estimates for CL and Vd were 4.53 l h(-1) and 27.3 l, respectively. The half-life of tobramycin was estimated to be 4.2 h. The inter-individual variability in CL and Vd were 37.0 and 28.5%, respectively. The residual error was 1.2 mg l(-1). Based on the results, optimal dosing intervals for renal impaired patients were calculated and were comparable with the intervals derived from the previous established nomogram.
    International Journal of Antimicrobial Agents 09/2000; 15(3):185-91. DOI:10.1016/S0924-8579(00)00172-2 · 4.30 Impact Factor
  • C O Onyeji · D P Nicolau · C H Nightingale · L Bow ·
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    ABSTRACT: It has been demonstrated previously that, in non-neutropenic animals, interferon-gamma markedly enhances the efficacies of gentamicin and vancomycin against Enterococcus faecalis resistant to these antibiotics. The aim of our study was to determining whether granulocyte colony-stimulating factor (G-CSF) can be beneficial as an adjunct to gentamicin and vancomycin in the treatment of the same infection in neutropenic mice. After induction of neutropenia by cyclophosphamide, mice were inoculated ip with the organism. The infected animals received sc administrations of G-CSF, antibiotic or a combination of both agents at determined dosing regimens. Infected animals treated with G-CSF alone showed a dose-dependent increase in survival. The inoculum size used in establishing infection affected the effectiveness of the cytokine. Survival was significantly (P: < 0.01) better in the infected animals given gentamicin and vancomycin plus G-CSF than in those given antibiotics or G-CSF alone. The possibility of pharmacokinetic interaction between G-CSF and each of the antibiotics was examined. The cytokine significantly increased the plasma clearance of gentamicin, with a resultant decrease in the area under the concentration-time curve (AUC), while the disposition of vancomycin was not affected. This study suggests that G-CSF may be a useful adjunct to gentamicin and vancomycin for the treatment of multidrug-resistant E. faecalis infection in neutropenic patients.
    Journal of Antimicrobial Chemotherapy 09/2000; 46(3):429-36. DOI:10.1093/jac/46.3.429 · 5.31 Impact Factor
  • E M Grant · M K Zhong · P G Ambrose · D P Nicolau · C H Nightingale · R Quintiliani ·

    American Journal of Health-System Pharmacy 06/2000; 57(10):992-5. · 1.88 Impact Factor
  • M K Kim · D P Nicolau · C H Nightingale · R Quintiliani ·

    Connecticut medicine 05/2000; 64(4):209-12.
  • C H Nightingale ·
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    ABSTRACT: This study evaluated the quality of 11 generic clarithromycin products obtained in Poland, Slovakia, Slovenia, or Israel and manufactured in Slovenia or Israel. The generic products were examined visually, assayed by high-pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories. Fifty-five percent of generic products fell short of the specifications for the innovator product. Ten percent of the generic products did not contain the amount of clarithromycin claimed in the label; 18% released less drug than did the branded tablets in the standard dissolution assay. In light of these results, it is not possible to conclude that all generic tablets are of the same quality as the innovator product; clinical trial results achieved with branded clarithromycin should not be extrapolated to generic products.
    Advances in Therapy 05/2000; 17(3):167-78. DOI:10.1007/BF02853159 · 2.27 Impact Factor
  • J McNabb · R Quintiliani · D P Nicolau · E.D. Grant · C H Nightingale ·

    Current clinical topics in infectious diseases 02/2000; 20(20):24-42.
  • K Q Bui · MA Banevicius · C H Nightingale · R Quintiliani · D P Nicolau ·
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    ABSTRACT: Recent in vitro and in vivo data have substantiated the beneficial effects of macrolides/ azalides for use against Pseudomonas aeruginosa. While macrolides/azalides are not very potent in vitro antimicrobial agents against this pathogen, they appear to have an adjunctive role by either altering the course of infection owing to their inhibition of biofilm production or modulation of the host anti-inflammatory response, or both. To determine the in vitro and in vivo effects of clarithromycin as adjunctive therapy with ceftazidime against a mucoidproducing strain of P. aeruginosa, we performed a standard time-kill experiment and a pneumonia model in mice, respectively. Time-kill studies were performed over a 24 h period with varying concentrations of clarithromycin and ceftazidime alone or in combination. Synergic activity was noted with the use of 0.5 x MIC of ceftazidime combined with either 0.5 or 2 x MIC of clarithromycin. Neutropenic mice were infected with 10(8) cfu of mucoid P. aeruginosa intranasally to produce pneumonia and subsequently treated with oral clarithromycin (100 mg/kg) and/or sc ceftazidime (1500 mg/kg) as monotherapy or in combination. The addition of 5 days of clarithromycin to the ceftazidime regimen significantly improved survival as compared with the beta-lactam alone (48% versus 32%, P = 0.04). While a statistically significant difference was not detected with the addition of 3 days of clarithromycin therapy, a trend towards improved survival was noted with this regimen (38% versus 32%). These data demonstrate the adjunctive potential of clarithromycin when administered in combination with an antipseudomonal agent for the treatment of mucoid-producing Pseudomonas in acute respiratory infection.
    Journal of Antimicrobial Chemotherapy 02/2000; 45(1):57-62. DOI:10.1093/jac/45.1.57 · 5.31 Impact Factor
  • Source
    D P Nicolau · M A Banevicius · C H Nightingale · R Quintiliani ·
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    ABSTRACT: While a time-kill methodology noted no appreciable improvement in bactericidal activity with the addition of azithromycin (AZM) to a ceftazidime (CAZ) regimen, data from the murine pneumonia model showed that the addition of AZM significantly improved survival compared to treatment with CAZ alone. These data suggest that AZM might be a useful adjunctive therapy in the management of pneumonia resulting from mucoid isolates of Pseudomonas aeruginosa.
    Antimicrobial Agents and Chemotherapy 01/2000; 43(12):3033-5. · 4.48 Impact Factor
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    M K Lacy · D P Nicolau · C H Nightingale · A Geffken · R Teng · J Vincent · R Quintiliani ·
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    ABSTRACT: Trovafloxacin pharmacokinetics were evaluated in 12 subjects with AIDS. By using a randomized design, single 200-mg doses of oral trovafloxacin and intravenous alatrofloxacin were administered. The mean absolute bioavailability was 91%. The pharmacokinetics of trovafloxacin when administered orally as the active form or intravenously as the prodrug (alatrofloxacin) are not altered in subjects with AIDS compared to those in healthy adults.
    Antimicrobial Agents and Chemotherapy 01/2000; 43(12):3005-7. · 4.48 Impact Factor
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    K Q Bui · J McNabb · C Li · C H Nightingale · D P Nicolau ·
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    ABSTRACT: The intracellular dispositions of clarithromycin and azithromycin in AIDS patients requiring Mycobacterium avium complex (MAC) prophylaxis were studied. The dispositions of both drugs in mononuclear and polymorphonuclear leukocytes were markedly different. Our data support the proven efficacy of these agents for MAC prophylaxis since clarithromycin and azithromycin displayed sustained intracellular concentrations which exceeded their MICs for MAC throughout the dosing periods.
    Antimicrobial Agents and Chemotherapy 10/1999; 43(9):2302-4. · 4.48 Impact Factor
  • Nicolau D.P · JoCarol McNabb · Lacy M.K · Jing Li · Richard Quintiliani · Nightingale C.H ·
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    ABSTRACT: Objective: This study aimed too compare the pharmacokinetic and pharmacodynamic profile of intermittent and continuously infused ceftazidime in patients with nosocomial pneumonia. Design and Setting: Prospective, randomised study set in a large community-teaching hospital. Interventions: Thirty-four patients receiving ceftazidime either as an intermittent infusion or a continuous infusion underwent blood sampling for drug concentration determinations between days 2 to 5 of therapy. In addition, at study enrolment sputum samples were obtained for Gram’s stain and culture. The minimum inhibitory concentration (MIC) of isolated organisms to ceftazidime was determined using the broth microdilution technique. Main Outcome Measures: Pharmacokinetic parameters were derived individually for each patient. The pharmacodynamic profile of ceftazidime was assessed as the duration of time the serum concentration remained above the MIC (T > MIC) of the organism(s) for each regimen. Results: Patients were well matched for demographic variables. The pharmacokinetic parameter estimates (mean ± SD) for patients receiving the intermittent infusion therapy were as follows: maximum concentration in serum 106.5 ± 34.6 mg/L; half-life 3.2 ± 2.5 hours; total body clearance (CLt) 142.5 ± 59 ml/min. The steady-state concentration with the continuous infusion regimen was 17.4 ± 6.1 mg/L, while the CLt was similar at 133.2 ± 37 ml/min. Forty-six pathogens were isolated in 27 patients. The continuous infusion regimen maximised the pharmacodynamics of ceftazidime as T > MIC was 100% of the dosage interval in all patients, whereas the intermittent infusion regimens resulted in T > MIC values of 56 to 100%. Conclusions: In critically ill patients with nosocomial pneumonia the administration of ceftazidime by continuous infusion appears to optimise the pharmacodynamic profile of this β-lactam by constantly providing concentrations in excess of the MIC of susceptible organisms over the course of therapy.
    Clinical Drug Investigation 07/1999; 18(2):133-139. DOI:10.2165/00044011-199918020-00006 · 1.56 Impact Factor
  • E Grant · D P Nicolau · C H Nightingale · R Quintiliani ·

    Connecticut medicine 06/1999; 63(5):275-7.
  • Source
    A C Keung · R C Owens · M G Eller · S J Weir · D P Nicolau · C H Nightingale ·
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    ABSTRACT: Rifapentine is undergoing development for the treatment of pulmonary tuberculosis. This study was conducted to characterize the single-dose pharmacokinetics of rifapentine and its 25-desacetyl metabolite and to assess the effect of food on the rate and extent of absorption in participants infected with human immunodeficiency virus (HIV). Twelve men and four women, mean age, 38.6 +/- 6.9 years, received a single 600-mg oral dose of rifapentine in an open-label, randomized two-way, complete crossover study. Each volunteer received rifapentine following a high-fat breakfast or during a fasting period. Serial blood samples were collected for 72 h and both rifapentine and its metabolite were assayed by a validated high-performance liquid chromatography method. Pharmacokinetics of rifapentine and 25-desacetylrifapentine were determined by noncompartmental methods. Mean (+/- the standard deviation) maximum concentrations of rifapentine in serum and areas under the curve from time zero to infinity following a high-fat breakfast were 14.09 +/- 2.81 and 373.63 +/- 78.19 micrograms/ml, respectively, and following a fasting period they were 9.42 +/- 2.67 and 256.10 +/- 86.39 micrograms. h/ml, respectively. Pharmacokinetic data from a previously published healthy volunteer study were used for comparison. Administration of rifapentine with a high-fat breakfast resulted in a 51% increase in rifapentine bioavailability, an effect also observed in healthy volunteers. Although food increased the exposure of these patients to rifapentine, the infrequent dosing schedule for the treatment of tuberculosis (e.g., once- or twice-weekly dosing) would be unlikely to lead to accumulation. Additionally, autoinduction has been previously studied and has not been demonstrated with this compound, unlike with rifabutin and rifampin. Rifapentine was well tolerated by HIV-infected study participants. The results of our study suggest that no dosage adjustments may be required for rifapentine in HIV-infected patients (Centers for Disease Control and Prevention classification A1, A2, B1, or B2) undergoing treatment for tuberculosis.
    Antimicrobial Agents and Chemotherapy 06/1999; 43(5):1230-3. · 4.48 Impact Factor

Publication Stats

3k Citations
606.57 Total Impact Points


  • 1975-2006
    • Hartford Hospital
      • Department of Medicine
      Hartford, Connecticut, United States
  • 1999
    • Kansas City VA Medical Center
      Kansas City, Missouri, United States
  • 1977-1999
    • University of Connecticut
      • School of Pharmacy
      Сторс, Connecticut, United States
  • 1996
    • Long Island University
      • Division of Pharmacy Practice
      New York City, New York, United States
  • 1994-1995
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
    • Butler University
      Indianapolis, Indiana, United States
    • University of Hartford
      West Hartford, Connecticut, United States
  • 1988
    • University of Rhode Island
      • College of Pharmacy
      Кингстон, Rhode Island, United States
  • 1978
    • University at Buffalo, The State University of New York
      • Department of Medicine
      Buffalo, New York, United States