Effects of valproic acid coadministration on plasma efavirenz and lopinavir concentrations in human immunodeficiency virus-infected adults

被引:43
作者
DiCenzo, R
Peterson, D
Cruttenden, M
Morse, G
Riggs, G
Gelbard, H
Schifitto, G
机构
[1] Univ Rochester, Med Ctr, Clin Pharmacol Unit, Rochester, NY 14642 USA
[2] SUNY Buffalo, Buffalo, NY USA
关键词
D O I
10.1128/AAC.48.11.4328-4331.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Valproic acid (VPA) has the potential to benefit patients suffering from human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine if VPA affects the plasma concentration of efavirenz (EFV) or lopinavir. HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir-ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing interval at steady state before and after receiving 250 mg of VPA twice daily for 7 days. VPA blood samples drawn before (C.) and 8 h after the morning dose (8 h) were compared to blood samples from a group of HIV-1-infected subjects who were taking either combined nucleoside reverse transcriptase inhibitors alone or had discontinued antiretroviral therapy. Pharmacokinetic parameters were calculated by noncompartmental analysis, and tests of bioequivalence were based on 90% confidence intervals (CIs) for ratios or differences. The geometric mean ratio (GMR) (90% CI) of the areas under the concentration-time curve from 0 to 24 h (AUC(0-24)s) of EFV (n = 11) with and without VPA was 1.00 (0.85, 1.17). The GMR (90% CI) of the AUC(0-8)s of LPV (n = 8) with and without VPA was 1.38 (0.98, 1.94). The differences (90% CI) in mean C(0) and 8-h VPA concentrations versus the control (n = 11) were -1.0 (-9.4, 7.4) mug/ml and -2.1 (-11.1, 6.9) mug/ml for EFV (n = 10) and -5.0 (-13.2, 3.3) mug/ml and -6.7 (-17.6, 4.2) mug/ml for LPV/r (n = 11), respectively. EFV administration alone is bioequivalent to EFV and VPA coadministration. LPV concentrations tended to be higher when the drug was combined with VPA. Results of VPA comparisons fail to raise concern that coadministration with EFV or LPV/r will significantly influence trough concentrations of VPA.
引用
收藏
页码:4328 / 4331
页数:4
相关论文
共 37 条
[1]   Position paper on therapeutic drug monitoring of antiretroviral agents [J].
Acosta, EP ;
Gerber, JG .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2002, 18 (12) :825-834
[2]   NEURONAL APOPTOSIS IN HIV-INFECTION IN ADULTS [J].
ADLEBIASSETTE, H ;
LEVY, Y ;
COLOMBEL, M ;
PORON, F ;
NATCHEV, S ;
KEOHANE, C ;
GRAY, F .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 1995, 21 (03) :218-227
[3]   LORAZEPAM-VALPROATE INTERACTION - STUDIES IN NORMAL SUBJECTS AND ISOLATED-PERFUSED RAT-LIVER [J].
ANDERSON, GD ;
GIDAL, BE ;
KANTOR, ED ;
WILENSKY, AJ .
EPILEPSIA, 1994, 35 (01) :221-225
[4]   A mechanistic approach to antiepileptic drug interactions [J].
Anderson, GD .
ANNALS OF PHARMACOTHERAPY, 1998, 32 (05) :554-563
[5]   Therapeutic drug monitoring of nelfinavir and indinavir in treatment-naive HIV-1-infected individuals [J].
Burger, D ;
Hugen, P ;
Reiss, P ;
Gyssens, I ;
Schneider, M ;
Kroon, F ;
Schreij, G ;
Brinkman, K ;
Richter, C ;
Prins, J ;
Aarnoutse, R ;
Lange, J .
AIDS, 2003, 17 (08) :1157-1165
[6]   THE LACK OF EFFECT OF SODIUM VALPROATE ON THE PHARMACOKINETICS OF ORAL-CONTRACEPTIVE STEROIDS [J].
CRAWFORD, P ;
CHADWICK, D ;
CLELAND, P ;
TJIA, J ;
COWIE, A ;
BACK, DJ ;
ORME, ML .
CONTRACEPTION, 1986, 33 (01) :23-29
[7]   INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B [J].
CROSS, DAE ;
ALESSI, DR ;
COHEN, P ;
ANDJELKOVICH, M ;
HEMMINGS, BA .
NATURE, 1995, 378 (6559) :785-789
[8]  
Crowder RJ, 1998, J NEUROSCI, V18, P2933
[9]   Indinavir, efavirenz, and abacavir pharmacokinetics in human immunodeficiency virus-infected subjects [J].
DiCenzo, R ;
Forrest, A ;
Squires, KE ;
Hammer, SM ;
Fischl, MA ;
Wu, HL ;
Cha, R ;
Morse, GD .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (06) :1929-1935
[10]  
Dou HY, 2003, J NEUROSCI, V23, P9162