The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids

Crawford, Pamela; Chadwick, David; Cleland, P. G.; Tjia, John; Cowie, A.; Back, DJ; Orme, M.

doi:10.1016/0010-7824(86)90028-4

Cited by 79 publications

(26 citation statements)

References 10 publications

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“…In contrast to enzyme-inducing AEDs and lamotrigine, a study of six women has suggested that VPA may not lower COC hormone levels. 12 By way of mechanism, it has been suggested that estrogen-induced glucuronidation might be responsible for the drop in AED levels during active COC use and the restoration of AED levels over a few days off active pill. 7-10 Different types of estrogen vary in their enzyme induction potential.…”

Section: Resultsmentioning

confidence: 99%

Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use

Herzog

Blum²,

Farina³

et al. 2009

Neurology

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The findings suggest that valproate (VPA), like lamotrigine (LTG), has substantially and significantly lower serum levels while women take active combined oral contraceptives as compared to inactive pills. Larger sample sizes will be required to determine whether LTG levels may drop significantly also during the luteal (high steroid) phase of natural menstrual cycles and whether VPA levels may show greater stability in levels across the phases of the menstrual cycle.

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Section: Resultsmentioning

confidence: 99%

Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use

Herzog

Blum²,

Farina³

et al. 2009

Neurology

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“…VPA has also been shown to inhibit the UGT-mediated metabolism of drugs such as zidovudine, lamotrigine, and lorazepam (4,31,34,37). VPA does not inhibit the metabolism of CYP 3A-dependent drugs such as cyclosporine and oral contraceptives, suggesting a lack of influence on CYP 3A-dependent metabolism (6,17). Being highly bound to albumin, VPA also has the ability to interact with other drugs via protein displacement; however, PIs are thought to be primarily bound to alpha-1-acid glycoprotein, minimizing the potential for protein displacement by VPA (22,31).…”

Section: Discussionmentioning

confidence: 99%

Effects of Valproic Acid Coadministration on Plasma Efavirenz and Lopinavir Concentrations in Human Immunodeficiency Virus-Infected Adults

DiCenzo

Peterson

Cruttenden

et al. 2004

Antimicrob Agents Chemother

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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 lopinavirritonavir (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 0 ) 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) g/ml and ؊2.1 (؊11.1, 6.9) g/ml for EFV (n ‫؍‬ 10) and ؊5.0 (؊13.2, 3.3) g/ml and ؊6.7 (؊17.6, 4.2) g/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.

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“…These AEDs do not significantly alter the pharmacokinetics of contraceptive estrogens and progestins (15,16,(30)(31)(32). Based on the findings in our study, LEV also may be included in this third group of AEDs.…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

Ragueneau‐Majlessi

Levy

Janik³

2002

Epilepsia

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Summary:Purpose: This study was designed to evaluate whether levetiracetam, a novel antiepileptic drug (AED), influences the pharmacokinetics of steroid oral contraceptives.Methods: During a run-in phase, 18 healthy female patients received an oral contraceptive containing ethinyl estradiol, 0.03 mg, and levonorgestrel, 0.15 mg, for the first 21 days of two consecutive menstrual cycles. In a subsequent double-blind, randomized, two-way crossover treatment phase, subjects received either levetiracetam, 500 mg, or placebo twice daily concomitant with the oral contraceptive. Plasma concentrations of ethinyl estradiol and levonorgestrel were measured on days 14 and 15 of the two treatment periods for the evaluation of the 24-h kinetic parameters, and an additional sample was collected on day 21 to determine the trough plasma concentrations. Serum progesterone and luteinizing hormone (LH) levels were determined on days 13, 14, 15, and 21 of each cycle of the treatment phase.Results: The plasma concentration-time curves and pharmacokinetic parameters of ethinyl estradiol and levonorgestrel were not statistically different during concomitant treatment with either levetiracetam or placebo. The ratios of the logtransformed geometric mean areas under the plasma concentration-time curves (AUCs), maximal (C max ) and minimal (C min ) plasma concentrations, and trough concentrations on day 21 (C 21 ) ranged from 99.12 to 99.96% for ethinyl estradiol and from 97.13 to 99.41% for levonorgestrel. The 90% confidence intervals of these ratios were well within the 80 to 125% acceptance range for lack of interaction. Serum progesterone and LH concentrations were fairly constant during the run-in and treatment phases and remained markedly below their respective physiologic levels. Safety and menstrual-bleeding patterns were comparable during levetiracetam and placebo administration.Conclusions: Levetiracetam does not affect the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and levonorgestrel, and on the basis of serum progesterone and LH levels, it does not affect the contraceptive efficacy.

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The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids

Cited by 79 publications

References 10 publications

Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use

Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use

Effects of Valproic Acid Coadministration on Plasma Efavirenz and Lopinavir Concentrations in Human Immunodeficiency Virus-Infected Adults

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

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