scholarly journals Lack of Pharmacokinetic Interaction between Enalapril and Amlodipine with Phenytoin in Rhesus monkeys

2004 ◽  
Vol 3 (3) ◽  
pp. 75
Author(s):  
SK Garg ◽  
DK Badyal ◽  
S Majumdar
Keyword(s):  
Rhesus Monkeys ◽  
Multiple Dose ◽  
Plasma Concentrations ◽  
Pharmacokinetic Interaction ◽  
Pharmacokinetic Parameters ◽  
Multiple Dose Study ◽  
Pharmacokinetic Interactions ◽  
Epileptic Patients ◽  
Dose Study

A cross-over and multiple dose study was carried out to find out possible pharmacokinetic interactions between phenytoin (DPH 35 ma/kg; p.o.) and antihypertensives enalapril (1.6 mg/kg; p.o.) and amlodipine (0.4 mg/kg, p.o.) in rhesus monkeys. Neither the plasma concentrations nor the pharmacokinetic parameters of DPH were altered by coadministration of enalapril or amlodipine, suggesting that enalapril and amlodipine can be safely administered to epileptic patients receiving phenytoin.

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

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

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

2009 ◽  
Vol 53 (9) ◽  
pp. 3720-3725 ◽  
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.

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

2009 ◽  
Vol 53 (11) ◽  
pp. 4840-4844 ◽  
Author(s):  
C. J. L. la Porte ◽  
J. P. Sabo ◽  
L. Béïque ◽  
D. W. Cameron
Keyword(s):  
Steady State ◽  
Multiple Dose ◽  
Healthy Adult ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Open Label ◽  
Multiple Dose Study ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Dose Study

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.

In vivo percutaneous absorption of chemicals: A multiple dose study in rhesus monkeys

1990 ◽  
Vol 28 (2) ◽  
pp. 129-132 ◽  
Author(s):  
D.A.W. Bucks ◽  
R.S. Hinz ◽  
R. Sarason ◽  
H.I. Maibach ◽  
R.H. Guy
Keyword(s):  
Percutaneous Absorption ◽  
Rhesus Monkeys ◽  
Multiple Dose ◽  
Multiple Dose Study ◽  
Dose Study ◽  
In Vivo Percutaneous Absorption

scholarly journals Pharmacokinetics, safety and tolerability of L-3-n-butylphthalide tablet after single and multiple oral administrations in healthy Chinese volunteers

2015 ◽  
Vol 51 (3) ◽  
pp. 525-531 ◽  
Author(s):  
Meng Wang ◽  
Quan-ying Zhang ◽  
Wen-yan Hua ◽  
Ming Huang ◽  
Wen-jia Zhou ◽  
...  
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Compartmental Analysis ◽  
Pharmacokinetic Parameters ◽  
Double Blind ◽  
Single Dose Study ◽  
Multiple Dose Study ◽  
Dose Study ◽  
Repeated Doses ◽  
Healthy Chinese

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.

scholarly journals INFLUENCE OF LOVASTATIN ON PHARMACOKINETICS AND PHARMACODYNAMICS OF GLIPIZIDE IN HEALTHY AND STREPTOZOTOCIN - INDUCED DIABETIC RATS: INVOLVEMENT OF P-GLYCOPROTEIN INHIBITION

2016 ◽  
Vol 9 (5) ◽  
pp. 3
Author(s):  
Kishore Kumar Kadimpati ◽  
Vanishree Sammeta ◽  
Ravindra Babu Pingili ◽  
Dr. Sujatha Sanneboina
Keyword(s):  
Multiple Dose ◽  
Diabetic Rats ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Glycoprotein P ◽  
Multiple Dose Study ◽  
P Glycoprotein ◽  
Dose Study ◽  
Glycoprotein Inhibition ◽  
Everted Sacs

ABSTRACTThis study evaluated the effect of lovastatin (Lov) on the pharmacokinetics and pharmacodynamics of glipizide (Gpz) in healthy and streptozotocininduceddiabeticrats.In singledose study(SDS), blood samples werecollectedonthe 1st day, whereas in multiple dose study on the 15 day at0-12 hrs. Lov significantly altered the pharmacokinetic parameters at the dose of 15 mg/kg in SDS and multiple dose study. The C of Gpz wasincreased from 2.97 to 8.38 and 9.87 to 24.58 ng/mL in healthy and diabetic rats, respectively, in multiple dose study. Rat everted sacs were used tostudy the transport of Gpz in the presence of Lov and verapamil (P-glycoprotein [P-gp] inhibitor). The transport of Gpz from mucosal to the serosalsurface was significantly increased from 4.32 to 5.65 and 6.02 µg/mL in the presence of Lov and verapamil, respectively. The interaction between Lovand Gpz is due to P-gp and CYP2C9 inhibition.Keywords: Diabetes, Dyslipidemia, Glipizide, Lovastatin, P-glycoprotein.maxth

Safety, Tolerability, and Pharmacokinetics of GDC-0276, a Novel NaV1.7 Inhibitor, in a First-in-Human, Single- and Multiple-Dose Study in Healthy Volunteers

2019 ◽  
Vol 39 (9) ◽  
pp. 873-887 ◽  
Author(s):  
Michael E. Rothenberg ◽  
Michael Tagen ◽  
Jae H. Chang ◽  
Janel Boyce-Rustay ◽  
Michel Friesenhahn ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Multiple Dose ◽  
Multiple Dose Study ◽  
Dose Study
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