Effect of mycophenolate mofetil on the pharmacokinetics of antiretroviral drugs and on intracellular nucleoside triphosphate pools.
Clin Pharmacokinet
; 43(12): 823-32, 2004.
Article
en En
| MEDLINE
| ID: mdl-15355127
ABSTRACT
OBJECTIVE:
To study the effect of mycophenolate mofetil therapy on the pharmacokinetic parameters of a number of antiretroviral drugs, on intracellular pools of deoxycytidine triphosphate (dCTP) and deoxyguanosine triphosphate (dGTP), and on intracellular concentrations of the triphosphate of lamivudine (3TCTP).DESIGN:
Randomised pharmacokinetic study.PARTICIPANTS:
Nineteen HIV-1-infected patients.METHODS:
Antiretroviral-naive men starting treatment with didanosine 400 mg once daily, lamivudine 150 mg twice daily, abacavir 300 mg twice daily, indinavir 800 mg twice daily, ritonavir 100 mg twice daily and nevirapine 200 mg twice daily were randomised to a group with or without mycophenolate mofetil 500 mg twice daily. After 8 weeks of therapy, the plasma pharmacokinetic profiles of mycophenolic acid (the active metabolite of mycophenolate mofetil), abacavir, indinavir and nevirapine, and triphosphate concentrations (dCTP, dGTP and 3TCTP) in peripheral blood mononuclear cells, were determined.RESULTS:
Nine of the 19 patients received mycophenolate mofetil. There was no difference in plasma clearance of indinavir or abacavir between the two groups. The clearance of nevirapine was higher in patients using mycophenolate mofetil (p = 0.04). In 12 patients, of whom five also received mycophenolate mofetil, intracellular triphosphates were measured. There was no significant difference in intracellular dCTP, dGTP or 3TCTP concentrations between the two groups.CONCLUSION:
In this small cohort of patients, mycophenolate mofetil therapy reduced the plasma concentration of nevirapine but had no effect on plasma concentrations of indinavir and abacavir. There were no consistent effects of mycophenolic acid on the intracellular concentrations of dCTP, dGTP or 3TCTP.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antiinflamatorios no Esteroideos
/
Síndrome de Inmunodeficiencia Adquirida
/
VIH-1
/
Lamivudine
/
Citidina Trifosfato
/
Antirretrovirales
/
Nucleótidos de Desoxicitosina
/
Nucleótidos de Desoxiguanina
/
Ácido Micofenólico
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Pharmacokinet
Año:
2004
Tipo del documento:
Article
País de afiliación:
Países Bajos