Lack of Effect of Efavirenz on the Pharmacokinetics of Tipranavir-Ritonavir in Healthy Volunteers

ABSTRACT Previously it has been shown that tipranavir-ritonavir (TPV/r) does not affect efavirenz (EFV) plasma concentrations. This study investigates the effect of steady-state EFV on steady-state TPV/r pharmacokinetics. This was a single-center, open-label, multiple-dose study of healthy adult female and male volunteers. TPV/r 500/200 mg twice a day (BID) was given with food for 24 days. After dosing with TPV/r for 10 days, EFV 600 mg once a day was added to the regimen. Intensive pharmacokinetic (PK) sampling was done on days 10 and 24. Validated bioanalytical high-pressure liquid chromatography-tandem mass spectrometry methods were used to determine plasma tipranavir (TPV), ritonavir (RTV), and EFV concentrations. Thirty-four subjects were entered into the study, and 16 subjects completed it. The geometric mean ratios (90% confidence intervals) for TPV and RTV area under the curves, C maxs, and C mins comparing TPV/r alone and in combination with EFV were 0.97 (0.87 to 1.09), 0.92 (0.81 to 1.03), and 1.19 (0.93 to 1.54) for TPV and 1.03 (0.78 to 1.38), 0.92 (0.65 to 1.30), and 1.04 (0.72 to 1.48) for RTV. Frequently observed adverse events were diarrhea, headache, dizziness, abnormal dreams, and rash. EFV had no effect on the steady-state PK of TPV or RTV, with the exception of a 19% increase in the TPV C min, which is not clinically relevant. TPV/r can be safely coadministered with EFV and without the need for a dose adjustment.

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Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies

Pharmacological Reports ◽

10.1007/s43440-021-00239-x ◽

2021 ◽

Vol 73 (2) ◽

pp. 604-614

Author(s):

Piotr J. Rudzki ◽

Katarzyna Jarus-Dziedzic ◽

Monika Filist ◽

Edyta Gilant ◽

Katarzyna Buś-Kwaśnik ◽

...

Keyword(s):

Confidence Intervals ◽

Multiple Dose ◽

Geometric Mean ◽

Plasma Concentrations ◽

Pharmacokinetic Parameters ◽

Human Pharmacokinetics ◽

Magnesium Ions ◽

Open Label ◽

Multiple Dose Study ◽

Dose Study

Abstract Background Magnesium ions (Mg2+) increase and prolong opioid analgesia in chronic and acute pain. The nature of this synergistic analgesic interaction has not yet been explained. Our aim was to investigate whether Mg2+ alter tramadol pharmacokinetics. Our secondary goal was to assess the safety of the combination. Methods Tramadol was administered to healthy Caucasian subjects with and without Mg2+ as (1) single 100-mg and (2) multiple 50-mg oral doses. Mg2+ was administered orally at doses of 150 mg and 75 mg per tramadol dosing in a single- and multiple-dose study, respectively. Both studies were randomized, open label, laboratory-blinded, two-period, two-treatment, crossover trials. The plasma concentrations of tramadol and its active metabolite, O-desmethyltramadol, were measured. Results A total of 25 and 26 subjects completed the single- and multiple-dose study, respectively. Both primary and secondary pharmacokinetic parameters were similar. The 90% confidence intervals for Cmax and AUC0-t geometric mean ratios for tramadol were 91.95–102.40% and 93.22–102.76%. The 90% confidence intervals for Cmax,ss and AUC0-τ geometric mean ratios for tramadol were 93.85–103.31% and 99.04–105.27%. The 90% confidence intervals for primary pharmacokinetic parameters were within the acceptance range. ANOVA did not show any statistically significant contribution of the formulation factor (p > 0.05) in either study. Adverse events and clinical safety were similar in the presence and absence of Mg2+. Conclusions The absence of Mg2+ interaction with tramadol pharmacokinetics and safety suggests that this combination may be used in the clinical practice for the pharmacotherapy of pain. Graphic abstract

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Pharmacokinetics of Rasagiline in Healthy Adult Chinese Volunteers with Various Genotypes: A Single-Center, Open-Label, Multiple-Dose Study

Clinical Drug Investigation ◽

10.1007/s40261-016-0380-4 ◽

2016 ◽

Vol 36 (5) ◽

pp. 369-376 ◽

Cited By ~ 2

Author(s):

Xia Chen ◽

Qian Zhao ◽

Ji Jiang ◽

Jian Liu ◽

Pei Hu

Keyword(s):

Multiple Dose ◽

Healthy Adult ◽

Single Center ◽

Open Label ◽

Multiple Dose Study ◽

Dose Study

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Pharmacokinetics of rosuvastatin in healthy Chinese volunteers living in China: A randomized, open-label, ascending single- and multiple-dose study

Clinical Therapeutics ◽

10.1016/j.clinthera.2010.03.015 ◽

2010 ◽

Vol 32 (3) ◽

pp. 575-587 ◽

Cited By ~ 7

Author(s):

Xue-Ning Li ◽

Hong-Rong Xu ◽

Wei-Li Chen ◽

Nan-Nan Chu ◽

Jun-Ren Zhu

Keyword(s):

Multiple Dose ◽

Open Label ◽

Multiple Dose Study ◽

Dose Study ◽

Healthy Chinese

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Pharmacokinetics, tolerability and safety of aripiprazole once-monthly in adult schizophrenia: An open-label, parallel-arm, multiple-dose study

Schizophrenia Research ◽

10.1016/j.schres.2013.06.041 ◽

2013 ◽

Vol 150 (1) ◽

pp. 281-288 ◽

Cited By ~ 55

Author(s):

Suresh Mallikaarjun ◽

John M. Kane ◽

Patricia Bricmont ◽

Robert McQuade ◽

William Carson ◽

...

Keyword(s):

Multiple Dose ◽

Open Label ◽

Multiple Dose Study ◽

Dose Study

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An in Vivo Single- and Multiple-Dose Study of Several Marketed Brands of Conventional and Controlled-Release Theophylline

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808401800212 ◽

1984 ◽

Vol 18 (2) ◽

pp. 147-153 ◽

Cited By ~ 3

Author(s):

Jeffrey A. Kotzan ◽

Joseph V. Vallner ◽

James T. Stewart ◽

Irwin L. Honigberg ◽

W.J. Brown

Keyword(s):

Single Dose ◽

Controlled Release ◽

Multiple Dose ◽

Healthy Adult ◽

Dosage Forms ◽

Adult Males ◽

Single Dose Study ◽

Multiple Dose Study ◽

Dose Study ◽

Release Tablet

In a single-dose study, 18 healthy adult males consumed each of six dosage forms of theophylline. A conventional-release tablet, a syrup, and four competing brands of controlled-release theophylline were studied. Serial serum samples were obtained and analyzed via high pressure liquid chromatography (HPLC). After achieving steady state, 15 healthy adult males consumed each of five dosage forms of theophylline in a multiple-dose study. Serial blood samples were obtained between 0 and 72 hours and subjected to analysis with HPLC. The results indicated that the controlled-release products were not bioequivalent, although they achieved longer time-to-peak values than did the immediate-release syrup and the conventional-release tablet. A single sustained-release product was uniquely different on most pharmacokinetic parameters when compared with the remaining three controlled-release products. In general, the dosage form variation exceeded the individual subject variation on the single-dose study, but the opposite was true for the multiple-dose study.

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