Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

In silico prediction of e… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

In silico prediction of efavirenz and rifampicin drug-drug interaction considering weight and CYP2B6 phenotype

Artikel i vetenskaplig tidskrift
Författare Dinko Rekić
Daniel Röshammar
Jackson Mukonzo
Michael Ashton
Publicerad i British Journal of Clinical Pharmacology
Volym 71
Nummer/häfte 4
Sidor 536-43
ISSN 0306-5251
Publiceringsår 2011
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 536-43
Språk en
Länkar dx.doi.org/10.1111/j.1365-2125.2010...
Ämnesord efavirenz;drug-drug interaction;rifampicin;in vitro in vivo extrapolation;Simcyp;HIV/AIDS;Anti-HIV Agents, pharmacokinetics, therapeutic use, Antibiotics, Antitubercular, pharmacokinetics, therapeutic use, Aryl Hydrocarbon Hydroxylases, genetics, Benzoxazines, pharmacokinetics, therapeutic use, Body Weight, drug effects, Computer Simulation, Dose-Response Relationship, Drug, Drug Interactions, Drug Therapy, Combination, Forecasting, methods, HIV Infections, drug therapy, genetics, Humans, Models, Theoretical, Oxidoreductases, N-Demethylating, genetics, Phenotype, Rifampin, pharmacokinetics, therapeutic use, Tuberculosis, drug therapy, genetics
Ämneskategorier Numerisk analys, Matematisk statistik, Biofarmaci, Klinisk farmakologi, Farmaceutisk farmakologi, Infektionsmedicin

Sammanfattning

Aims: To test whether a pharmacokinetic simulation model could extrapolate non-clinical drug data to predict human efavirenz exposure after single and continuous dosing as well as the effects of concomitant rifampicin and further to evaluate the weight based dosage recommendations used to counteract the rifampicin-efavirenz interaction. Methods: Efavirenz pharmacokinetics were simulated using a physiologically-based pharmacokinetic model implemented in the Simcyp population-based simulator. Physicochemical and metabolism data obtained from the literature were used as input for prediction of pharmacokinetic parameters. The model was used to simulate the effects of rifampicin on efavirenz pharmacokinetics in 400 virtual patients, taking into account bodyweight and CYP2B6 phenotype. Results: Apart from the absorption phase, the simulation model predicted efavirenz concentration-time profiles reasonably well with close agreement with clinical data. The simulated effects of rifampicin co-administration on efavirenz treatment showed only a minor decrease of 16% (95%CI 13; 19) in efavirenz area under the concentration-time curve (AUC), in magnitude with what has been clinically observed (22%). Efavirenz exposure depended on CYP2B6 phenotype and bodyweight. Increasing the efavirenz dose during concomitant rifampicin was predicted to be most successful in patients over 50 kg regardless of CYP2B6 status. Conclusion: Our findings, although based on a simulation approach using limited in vitro data, support the current recommendations for using a 50 kg bodyweight cut-off for efavirenz dose increment when co-treating with rifampicin.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?