Till sidans topp

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

Tipsa en vän
Utskriftsversion

HIV/AIDS Patients Display… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

HIV/AIDS Patients Display Lower Relative Bioavailability of Efavirenz than Healthy Subjects.

Artikel i vetenskaplig tidskrift
Författare Jackson K Mukonzo
Sarah Nanzigu
Dinko Rekić
Paul Waako
Daniel Röshammar
Michael Ashton
Jasper Ogwal-Okeng
Lars L Gustafsson
Eleni Aklillu
Publicerad i Clinical pharmacokinetics
Volym 50
Nummer/häfte 8
Sidor 531-40
ISSN 0312-5963
Publiceringsår 2011
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 531-40
Språk en
Länkar dx.doi.org/10.2165/11592660-0000000...
Ämneskategorier Farmakologi och toxikologi, Klinisk farmakologi, Farmaceutisk farmakologi, Internationell Migration och Etniska Relationer (IMER)

Sammanfattning

Background: Pharmacokinetic studies of antiretroviral drugs are often conducted in adult healthy subjects, and the results are extrapolated to HIV/AIDS patients. HIV/AIDS, however, is known to cause morphological and physiological changes that may alter the pharmacokinetics of antiretroviral drugs. We examined the effect of HIV/AIDS on the pharmacokinetics of efavirenz in Ugandans. Methods: After a first oral dose of efavirenz 600 mg in treatment-naïve HIV-infected patients, blood samples were collected at nine time points up to 24 hours. The plasma-concentration time data from these patients were merged with previously reported data from adult healthy subjects. Population pharmacokinetic models were fitted to the data, using NONMEM VI software. Covariate analyses were performed to estimate the effects of HIV/AIDS disease, demographic characteristics (sex, bodyweight, age), biochemical variables (serum creatinine, urea, alanine aminotransferase) and pharmacogenetic variation in cytochrome P450 (CYP) 2B6, CYP3A5 and adenosine triphosphate-binding cassette, sub-family B, member 1 (ABCB1) on the population pharmacokinetic parameters. Results: Efavirenz plasma concentration-time data obtained from 29 HIV-1-infected, treatment-naïve patients were merged with previously reported data from 32 adult healthy subjects. The model identified sex and HIV/AIDS disease as statistically significant categorical predictors of efavirenz pharmacokinetics. Females were predicted to have a 2-fold higher volume of distribution of the peripheral compartment after oral administration (V(2)/F) than males (95% CI 1.53, 2.63), while HIV/AIDS patients were found to have 30% lower relative bioavailability (95% CI 18.7, 40.7) than healthy subjects. The increased V(2)/F in females resulted in a 2-fold longer elimination half-life than in males. Conclusion: On the basis of the findings of this analysis, we conclude that, apart from bodyweight-based differences, both HIV/AIDS disease and sex affect efavirenz pharmacokinetics in Ugandans. HIV/AIDS disease is associated with reduced relative bioavailability of efavirenz. We recommend that findings from healthy subject studies be confirmed in HIV/AIDS patients and that caution be applied in direct extrapolation of exposure data to the target patient population.

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?