Effect of Orlistat, a Novel Anti-Obesity Agent, on the Pharmacokinetics and Pharmacodynamics of Pravastatin in Patients with Mild Hypercholesterolaemia

Oo, Charles; Akbari, Bardia; Nichols, G. Michael; Hellmann, C

doi:10.2165/00044011-199917030-00006

Cited by 12 publications

(4 citation statements)

References 16 publications

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“…itant drugs (especially those with narrow therapeutic indices), fat-soluble vitamins, and alcohol. [3][4][5][6][7][8][9][10][11][12][13][14][15] Orlistat has been shown for reducing the bioavailability of a few highly lipophilic substances such as cyclosporine, 15 vitamin E, 11 and β-carotene. 10 The objective of the three studies in this report was to extend, from previous studies, the investigation of the influence of orlistat on the pharmacokinetics of highly lipophilic drugs (octanol/water partition coefficient greater than 10,000).…”

Section: • J Clin Pharmacol 2003;43:428-435mentioning

confidence: 99%

“…On the other hand, due to its mechanism of action, there is a potential for orlistat to affect the absorption of concomitant, fat‐soluble drugs and nutrients. Numerous interaction studies have been carried out to evaluate potential interactions between orlistat and concomitant drugs (especially those with narrow therapeutic indices), fat‐soluble vitamins, and alcohol 3–15 . Orlistat has been shown for reducing the bioavailability of a few highly lipophilic substances such as cyclosporine, 15 vitamin E, 11 and β‐carotene 10 …”

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confidence: 99%

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Effects of Orlistat, a Lipase Inhibitor, on the Pharmacokinetics of Three Highly Lipophilic Drugs (Amiodarone, Fluoxetine, and Simvastatin) in Healthy Volunteers

Zhi

Moore

Kanitra

et al. 2003

The Journal of Clinical Pharma

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To investigate the effect of orlistat on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin), the authors performed double-blind, placebo-controlled, randomized two-period crossover (for fluoxetine and simvastatin) or parallel (for amiodarone) studies in healthy volunteers ages 18 to 65 years of a body mass index between 18 and 30 kg/m2. During treatment with orlistat or matching placebo for 5 to 13 1/3 days, a single oral dose of highly lipophilic drug was administered, followed by obtaining serial blood samples for measuring plasma (for fluoxetine and simvastatin) or serum (for amiodarone) concentrations of the lipophilic drug and its active metabolite. Treatments were compared for the pharmacokinetic parameters AUC0-infinity, Cmax, tmax, and t 1/2 of highly lipophilic drugs and active metabolites. Analysis of variance was performed to assess the significance of the sequence effect and provide the variance estimate for the 90% confidence intervals. Subjects were also evaluated for adverse events, vital signs, and clinical and laboratory safety. The absorption of amiodarone (and active metabolite) was significantly reduced by approximately one-quarter using parameters of Cmax and AUC, while no inhibition of absorption was observed for fluoxetine and simvastatin as well as their active metabolites. There were no clinically significant differences in t 1/2 and tmax for all three drugs tested. Due to expected gastrointestinal adverse events known to occur with orlistat, there was a higher incidence of adverse events under regimen B (highly lipophilic drugs and orlistat) than under regimen A (highly lipophilic drugs and placebo). Other adverse events were sporadic and unremarkable. There were no clinically relevant changes in vital signs or laboratory values. In conclusion, except for amiodarone, there was no effect of orlistat on the pharmacokinetics of highly lipophilic drugs when these drugs were taken concomitantly with orlistat.

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Section: • J Clin Pharmacol 2003;43:428-435mentioning

confidence: 99%

mentioning

confidence: 99%

Effects of Orlistat, a Lipase Inhibitor, on the Pharmacokinetics of Three Highly Lipophilic Drugs (Amiodarone, Fluoxetine, and Simvastatin) in Healthy Volunteers

Zhi

Moore

Kanitra

et al. 2003

The Journal of Clinical Pharma

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“…When logP is plotted against C max ratio and AUC ratio (Figure 1), both correlations appeared to follow an "inhibitory-effect sigmoidal E max " model, as illustrated in the above equation. Fitting the data in Table I into the equation yielded sets of useful parameters: for C max ratio, R max = 1.02 (2), 0.97 to 1.07; R min = 0.66 (5), 0.58 to 0.73; R 50 = 8.25 (9), 6.63 to 9.87; and γ = 10.00 (79), −6.72 to 26.72; for AUC ratio, R max = 0.99 (3), 0.94 to 1.05; R min = 0.59 (7), 0.51 to 0.67; R 50 = 8.3 (9), 6.6 to 9.9; and γ = 9.84 (78), −6.29 to 25.98, respectively. Results are reported as mean (percentage coefficient of variation), 95% confidence intervals.…”

Section: Resultsmentioning

confidence: 99%

Modeling the Relationship Between Drug Lipophilicity and Potential for an Interaction With Orlistat

Zhi

2012

The Journal of Clinical Pharma

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“…No pharmacodynamic or pharmacokinetic interactions were observed with orlistat 360 mg/day and warfarin (80) or glyburide (81) in healthy volunteers or with pravastatin in patients with mild hypercholesterolaemia (82). No pharmacokinetic interactions were reported with orlistat and digoxin (83), nifedipine (84) or phenytoin (85).…”

Section: Pre-absorptive Nutrient Partitioning: Orlistatmentioning

confidence: 90%

Recent and Future Drugs for the Treatment of Obesity

Gaal

Mertens

Leeuw

2001

International Textbook of Obesity

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Effect of Orlistat, a Novel Anti-Obesity Agent, on the Pharmacokinetics and Pharmacodynamics of Pravastatin in Patients with Mild Hypercholesterolaemia

Cited by 12 publications

References 16 publications

Effects of Orlistat, a Lipase Inhibitor, on the Pharmacokinetics of Three Highly Lipophilic Drugs (Amiodarone, Fluoxetine, and Simvastatin) in Healthy Volunteers

Effects of Orlistat, a Lipase Inhibitor, on the Pharmacokinetics of Three Highly Lipophilic Drugs (Amiodarone, Fluoxetine, and Simvastatin) in Healthy Volunteers

Modeling the Relationship Between Drug Lipophilicity and Potential for an Interaction With Orlistat

Recent and Future Drugs for the Treatment of Obesity

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