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The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir
(Les effets des cannabinoïdes sur la pharmacocinétique de l'indinavir et du nelfinavir.)
Auteur(s) :
KOSEL B. W. ;
AWEEKA, F. T. ;
BENOWITZ, N. L. ;
SHADE S. B. ;
HILTON, J. F. ;
LIZAK P. S. ;
ABRAMS, D. I.
Année
2002
Page(s) :
543-550
Langue(s) :
Anglais
Refs biblio. :
27
Domaine :
Drogues illicites / Illicit drugs
Discipline :
PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods)
Thésaurus mots-clés
CANNABINOIDES
;
ANTIRETROVIRAUX
;
USAGE THERAPEUTIQUE
;
VIH
;
EFFICACITE
;
PHARMACOCINETIQUE
Note générale :
AIDS, 2002, 16, (4), 543-550
Note de contenu :
fig. ; tabl.
Résumé :
FRANÇAIS :
Les effets métaboliques de la marijuana fumée et du dronabinol sont étudiés chez des patients infectés par le VIH qui reçoivent toutes les 8 heures soit 800 mg d'indinavir (n=38), soit 750 mg de nelfinavir (n=34). Les résultats montrent que les changements des paramètres induits par les cannabinoïdes n'ont pas de conséquences cliniques à court terme. L'usage de marijuana ou de dronabinol n'a pas d'impact sur l'efficacité des antiviraux.
ENGLISH :
Background and objectives: The use of cannabinoids for appetite stimulation and the management of wasting and antiretroviral side-effects has become a common practice in the care of HIV-infected individuals. We present pharmacokinetic data from a randomized placebo-controlled study designed to evaluate the metabolic effects of smoked marijuana and dronabinol in HIV-infected patients receiving indinavir (IDV) or nelfinavir (NFV). Methods: Subjects on stable regimens containing IDV 800 mg every 8 h (n = 28) or NFV 750 mg three time a day (n = 34) were randomized to one of three treatment arms: 3.95%, THC marijuana cigarettes, dronabinol 2.5 mg capsules or placebo capsules administered three times daily. Serial blood sampling was performed at baseline and on day 14 of treatment. The changes in NFV and IDV pharmacokinetics were measured as the median percentage change from baseline. Results: At day 14, the 8-h area under the curve (AUC8) changed by -10.2%, (P = 0.15), maximum concentration (Cmax) by -17.4% (P = 0.46), and minimum concentration (Cmin) by -12.2% (P = 0.28) for patients in the NFV marijuana arm (n = 11). Similar decreases had occurred by day 14 among patients in the IDV marijuana arm (n = 9): AUC8 had changed by - 14.5% (P = 0.074), Cmax by -14.1% (P = 0.039),and Cmin by -33.7%(P = 0,65). Conclusion: Despite a statistically significant decrease in Cmax of IDV in the marijuana arm, the magnitude of changes in IDV and NFV pharmacokinetic parameters in the marijuana arm are likely to have no short-term clinical consequence. The use of marijuana or dronabinol is unlikely to impact antiretroviral efficacy. (Author' s abstract)
Les effets métaboliques de la marijuana fumée et du dronabinol sont étudiés chez des patients infectés par le VIH qui reçoivent toutes les 8 heures soit 800 mg d'indinavir (n=38), soit 750 mg de nelfinavir (n=34). Les résultats montrent que les changements des paramètres induits par les cannabinoïdes n'ont pas de conséquences cliniques à court terme. L'usage de marijuana ou de dronabinol n'a pas d'impact sur l'efficacité des antiviraux.
ENGLISH :
Background and objectives: The use of cannabinoids for appetite stimulation and the management of wasting and antiretroviral side-effects has become a common practice in the care of HIV-infected individuals. We present pharmacokinetic data from a randomized placebo-controlled study designed to evaluate the metabolic effects of smoked marijuana and dronabinol in HIV-infected patients receiving indinavir (IDV) or nelfinavir (NFV). Methods: Subjects on stable regimens containing IDV 800 mg every 8 h (n = 28) or NFV 750 mg three time a day (n = 34) were randomized to one of three treatment arms: 3.95%, THC marijuana cigarettes, dronabinol 2.5 mg capsules or placebo capsules administered three times daily. Serial blood sampling was performed at baseline and on day 14 of treatment. The changes in NFV and IDV pharmacokinetics were measured as the median percentage change from baseline. Results: At day 14, the 8-h area under the curve (AUC8) changed by -10.2%, (P = 0.15), maximum concentration (Cmax) by -17.4% (P = 0.46), and minimum concentration (Cmin) by -12.2% (P = 0.28) for patients in the NFV marijuana arm (n = 11). Similar decreases had occurred by day 14 among patients in the IDV marijuana arm (n = 9): AUC8 had changed by - 14.5% (P = 0.074), Cmax by -14.1% (P = 0.039),and Cmin by -33.7%(P = 0,65). Conclusion: Despite a statistically significant decrease in Cmax of IDV in the marijuana arm, the magnitude of changes in IDV and NFV pharmacokinetic parameters in the marijuana arm are likely to have no short-term clinical consequence. The use of marijuana or dronabinol is unlikely to impact antiretroviral efficacy. (Author' s abstract)
Affiliation :
San Francisco Gen. Hosp., Drug Res. Unit, 1001 Potrero Ave., Bldg 100, San Francisco, CA 94110
Etats-Unis. United States.
Etats-Unis. United States.