Effects of Age and Sex on Single-Dose Pharmacokinetics of Tigecycline in Healthy Subjects

ABSTRACT The pharmacokinetics of tigecycline was evaluated in 46 healthy young and elderly men and women. Except for the volumes of distribution at steady state (approximately 350 liters in women versus 500 liters in men), there were no significant differences in tigecycline pharmacokinetic parameters. Based on pharmacokinetics, no dosage adjustment is warranted based on age or sex.

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Faculty Opinions recommendation of D₂-receptor occupancy measurement of JNJ-37822681, a novel fast off-rate D₂-receptor antagonist, in healthy subjects using positron emission tomography: single dose versus steady state and dose selection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717953114.793458670 ◽

2012 ◽

Author(s):

John Davis

Keyword(s):

Positron Emission Tomography ◽

Single Dose ◽

Steady State ◽

Receptor Antagonist ◽

Healthy Subjects ◽

Receptor Occupancy ◽

Emission Tomography ◽

Dose Selection ◽

Positron Emission

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Lack of Effect of Zafirlukast on the Pharmacokinetics of Azithromycin, Clarithromycin, and 14-Hydroxyclarithromycin in Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.5.1152 ◽

1999 ◽

Vol 43 (5) ◽

pp. 1152-1155 ◽

Cited By ~ 16

Author(s):

Kevin W. Garey ◽

Charles A. Peloquin ◽

Paul G. Godo ◽

Anne N. Nafziger ◽

Guy W. Amsden

Keyword(s):

Steady State ◽

Healthy Subjects ◽

High Performance ◽

Pharmacokinetic Parameters ◽

Steady State Concentration ◽

Open Label ◽

Time Curve ◽

Data Analyses ◽

Concentration Time ◽

State Concentration

ABSTRACT This randomized, open-label, crossover study was conducted to investigate whether the coadministration of zafirlukast would affect the pharmacokinetics of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC). Twelve healthy subjects (six males and six females) received single 500-mg doses of azithromycin and clarithromycin with and without zafirlukast given to a steady-state concentration. Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose, respectively. Serum was assayed for azithromycin, clarithromycin, and 14-OHC concentrations by validated high-performance liquid chromatography assay systems. Data analyses were done by noncompartmental and nonparametric methods. Analysis of the patients indicated that the addition of steady-state concentrations of zafirlukast did not significantly alter the pharmacokinetic parameters of or overall exposure (based on the area under the concentration-time curve) to azithromycin, clarithromycin, and 14-OHC. While zafirlukast is a known inhibitor of CYP3A4, it does not appear to exert a clinically or statistically significant pharmacokinetic effect on azithromycin, clarithromycin, or 14-OHC.

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Pharmacokinetics and Bioequivalence of Rasagiline Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions: An Open, Randomized, Single-Dose, Double-Cycle, Two-Sequence, Crossover Trial

Frontiers in Pharmacology ◽

10.3389/fphar.2020.571747 ◽

2020 ◽

Vol 11 ◽

Author(s):

Yinjuan Li ◽

Lu Qi ◽

Haihong Bai ◽

Ying Liu ◽

Rongxia Fan ◽

...

Keyword(s):

Single Dose ◽

Healthy Subjects ◽

Geometric Mean ◽

Pharmacokinetic Parameters ◽

Serious Adverse Events ◽

Good Tolerability ◽

Clinical Trial Registration ◽

Reference Drug ◽

Healthy Chinese ◽

Chinese Subjects

Objective: This study evaluated the pharmacokinetics, safety, and bioequivalence (BE) of two formulations of rasagiline tablets in healthy Chinese subjects under fasting and fed conditions.Methods: An open, randomized, single-dose, double-cycle, two-sequence, self-crossover pharmacokinetic study in healthy Chinese subjects under fasting and high-fat postprandial conditions was performed. A total of 108 healthy subjects (36 in the fasting group and 72 in the postprandial group) were recruited. In each cycle of the study under both conditions, subjects received a single oral dose of 1 mg of a test or reference preparation of rasagiline tablets (1 mg each). A washout period of 3 days was observed. Blood samples were obtained up to 10 h post-intake. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0–t and AUC0–∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters.Results: The 90% confidence interval (CI) of the geometric mean ratio (GMR) of the test drug vs. the reference drug for rasagiline was 94.16–105.35% for the AUC0–t under fasting conditions and 99.88–107.07% under postprandial conditions. The 90% CIs for the AUC0–∞ were 93.55–105.01% and 99.59–107.05% under fasting and postprandial conditions, respectively. The 90% CIs for the Cmax were 88.26–108.46% and 89.54–118.23% under fasting and postprandial conditions, respectively. The 90% CIs for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80–1.25) for BE. In this BE study, there were no serious adverse events (AEs).Conclusion: BE between the test and the reference products was established in both fasting and postprandial conditions. The two formulations of rasagiline showed good tolerability and a similar safety profile.Clinical Trial Registration:chinaDrugtrials.org.cn, identifier CTR20181466.

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Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00106-09 ◽

2009 ◽

Vol 53 (9) ◽

pp. 3720-3725 ◽

Cited By ~ 94

Author(s):

Ann M. Ginsberg ◽

Martino W. Laurenzi ◽

Doris J. Rouse ◽

Karl D. Whitney ◽

Melvin K. Spigelman

Keyword(s):

Mycobacterium Tuberculosis ◽

Single Dose ◽

Healthy Subjects ◽

Multiple Dose ◽

Pharmacokinetic Parameters ◽

Blood Levels ◽

Drug Resistant ◽

Single Dose Study ◽

Multiple Dose Study ◽

Dose Study

ABSTRACT PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis. The compound's MIC is between 0.015 and 0.25 μg/ml for drug-sensitive strains and between 0.03 and 0.53 μg/ml for drug-resistant strains. In addition, it is active against nonreplicating anaerobic Mycobacterium tuberculosis. The safety, tolerability, and pharmacokinetics of PA-824 were evaluated in two escalating-dose clinical studies, one a single-dose study and the other a multiple-dose study (up to 7 days of daily dosing). In 58 healthy subjects dosed with PA-824 in these studies, the drug candidate was well tolerated, with no significant or serious adverse events. In both studies, following oral administration PA-824 reached maximal plasma levels in 4 to 5 h independently of the dose. Maximal blood levels averaged approximately 3 μg/ml (1,500-mg dose) in the single-dose study and 3.8 μg/ml (600-mg dose) in the multiple-dose study. Steady state was achieved after 5 to 6 days of daily dosing, with an accumulation ratio of approximately 2. The elimination half-life averaged 16 to 20 h. Overall, PA-824 was well tolerated following oral doses once daily for up to 7 days, and pharmacokinetic parameters were consistent with a once-a-day regimen. The results of these studies, combined with the demonstrated activity of PA-824 against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis, support the investigation of this novel compound for the treatment of tuberculosis.

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Single-Dose Pharmacokinetics and Tolerability of Telavancin in Elderly Men and Women

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy ◽

10.1592/phco.30.8.806 ◽

2010 ◽

Vol 30 (8) ◽

pp. 806-811 ◽

Cited By ~ 13

Author(s):

Michael R Goldberg ◽

Shekman L Wong ◽

Jeng-Pyng Shaw ◽

Michael M Kitt ◽

Steven L Barriere

Keyword(s):

Single Dose ◽

Elderly Men ◽

Men And Women

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Pharmacokinetics of Telbivudine in Healthy Subjects and Absence of Drug Interaction with Lamivudine or Adefovir Dipivoxil

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01313-05 ◽

2006 ◽

Vol 50 (7) ◽

pp. 2309-2315 ◽

Cited By ~ 31

Author(s):

Xiao-Jian Zhou ◽

Barbara A. Fielman ◽

Deborah M. Lloyd ◽

George C. Chao ◽

Nathaniel A. Brown

Keyword(s):

Single Dose ◽

Steady State ◽

Plasma Concentration ◽

Healthy Subjects ◽

Adefovir Dipivoxil ◽

Geometric Mean ◽

Time Curve ◽

Concentration Time ◽

Plasma Pharmacokinetics ◽

Plasma Concentration Time Curve

ABSTRACT Two phase I studies were conducted to assess the plasma pharmacokinetics of telbivudine and potential drug-drug interactions between telbivudine (200 or 600 mg/day) and lamivudine (100 mg/day) or adefovir dipivoxil (10 mg/day) in healthy subjects. Study drugs were administered orally. The pharmacokinetics of telbivudine were characterized by rapid absorption with biphasic disposition. The maximum concentrations in plasma (C max) were reached at median times ranging from 2.5 to 3.0 h after dosing. Mean single-dose C max and area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) were 1.1 and 2.9 μg/ml and 7.4 and 21.8 μg · h/ml for the 200- and 600-mg telbivudine doses, respectively. Steady state was reached after daily dosing for 5 to 7 days. The mean steady-state C max and area under the plasma concentration-time curve over the dosing interval (AUCτ) were 1.2 and 3.4 μg/ml and 8.9 and 27.5 μg · h/ml for the 200- and 600-mg telbivudine repeat doses, respectively. The steady-state AUCτ of telbivudine was 23 to 57% higher than the single-dose values. Concomitant lamivudine or adefovir dipivoxil did not appear to significantly alter the steady-state plasma pharmacokinetics of telbivudine; the geometric mean ratios and associated 90% confidence interval (CI) for the AUCτ of telbivudine alone versus in combination were 106.3% (92.0 to 122.8%) and 98.6% (86.4 to 112.5%) when coadministered with lamivudine and adefovir dipivoxil, respectively. Similarly, the steady-state plasma pharmacokinetics of lamivudine or adefovir were not markedly affected by the coadministration of telbivudine; the geometric mean ratios and associated 90% CI, alone versus in combination with telbivudine, were 99.0% (87.1 to 112.4%) and 92.2% (84.0 to 101.1%), respectively, for the lamivudine and adefovir AUCτ values. Moreover, the combination regimens studied were well tolerated in all subjects. The results from these studies provide pharmacologic support for combination therapy or therapy switching involving telbivudine, lamivudine, and adefovir dipivoxil for the treatment of chronic hepatitis B virus infection.

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Pharmacokinetic evaluation of tapentadol extended-release tablets in healthy subjects

Journal of Opioid Management ◽

10.5055/jom.2013.0171 ◽

2013 ◽

Vol 9 (4) ◽

pp. 291-300 ◽

Cited By ~ 8

Author(s):

Peter N. Zannikos, PhD ◽

Johan W. Smit, PhD ◽

Hans-Jürgen Stahlberg, MD ◽

Birger Wenge, PhD ◽

Vera M. Hillewaert, MSc ◽

...

Keyword(s):

Single Dose ◽

Steady State ◽

Polyethylene Oxide ◽

Healthy Subjects ◽

Extended Release ◽

The United States ◽

Repeated Dose ◽

High Fat ◽

Japanese Men ◽

Fat Meal

Objective: To evaluate serum pharmacokinetics of tapentadol administered to healthy subjects as extended-release (ER) tablets.Design: Seven single-dose studies (five randomized, crossover, bioequivalence studies; a study in Japanese men; and a randomized, crossover, effects-of-food study) and one repeated-dose study.Setting: Clinical research settings in the United States and The Netherlands.Patients or participants: Healthy males and females were enrolled into seven studies; one study enrolled only Japanese males.Interventions: In the bioequivalence studies, subjects first received one polyethylene oxide- or hypromellose-based tapentadol ER tablet (50, 100, 150, 200, or 250 mg; one dose per study), then (after washout) the other formulation (matching dose). In all other studies, subjects received polyethylene oxide-based tapentadol ER tablets. In the repeated-dose study, subjects received one 250 mg tablet, then (after washout) one 250 mg tablet every 12 hours (five doses). In the food-effect study, subjects received one 250 mg tablet within 30 minutes after a high-fat meal or after 10 hours of fasting. In the study in Japanese men, subjects received one 100 mg tablet.Main outcome measures: Maximum tapentadol concentrations (Cmax) were typically observed 5 hours after dosing. Mean terminal half-life values ranged from 4.4 to 5.9 hours. Tapentadol Cmax and AUC values increased proportionally following single ER (polyethylene oxide-based tablets) doses of 50 to 250 mg. Trough tapentadol concentrations increased during repeat dosing until reaching steady-state by the third dose. Serum Cmax and area under the concentration-time curve (AUC) values at steady state were 1.6 and 1.9 times higher relative to singledose administration. Coadministration of the 250 mg dose with a high-fat meal increased Cmax and AUC values by an average of 17 percent.Conclusions: The pharmacokinetics of tapentadol ER are consistent after repeated and single-dose administration. Tapentadol ER may be administered without regard to food intake. No clinically significant differences were observed in the pharmacokinetics of tapentadol between Japanese and Caucasian subjects.

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