Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects

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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Evaluation of the potential for steady-state pharmacokinetic interaction between vildagliptin and simvastatin in healthy subjects

Current Medical Research and Opinion ◽

10.1185/030079907x233296 ◽

2007 ◽

Vol 23 (12) ◽

pp. 2913-2920 ◽

Cited By ~ 30

Author(s):

Surya P. Ayalasomayajula ◽

Kiran Dole ◽

Yan-Ling He ◽

Monica Ligueros-Saylan ◽

Yibin Wang ◽

...

Keyword(s):

Steady State ◽

Healthy Subjects ◽

Pharmacokinetic Interaction

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Lack of steady-state pharmacokinetic interaction of lescol XL® 80 mg and Norvasc® 5 mg in healthy subjects

American Journal of Hypertension ◽

10.1016/s0895-7061(01)01436-4 ◽

2001 ◽

Vol 14 (11) ◽

pp. A111

Author(s):

P Prasad

Keyword(s):

Steady State ◽

Healthy Subjects ◽

Pharmacokinetic Interaction

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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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