Impact of pregnancy on abacavir pharmacokinetics

Best, Brookie M.; Mirochnick, Mark; Capparelli, Edmund V.; Stek, Alice; Burchett, Sandra; Holland, Diane T.; Read, Jennifer S.; Smith, Elizabeth; Hu, Chengcheng; Spector, Stephen A.; Connor, James D.

doi:10.1097/01.aids.0000210609.52836.d1

Cited by 48 publications

(39 citation statements)

References 16 publications

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“…No covariate (age, body weight, pregnancy, or gestational age) had a significant effect on pharmacokinetics, so pregnant women and nonpregnant women had the same median population clearance values. This finding is consistent with the previous studies' reporting similar exposures between postpartum or nonpregnant women and pregnant women (10,11). The final population pharmacokinetics estimates are summarized in Table 1. …”

supporting

confidence: 90%

“…The median estimated value was 104% (minimum, 62%; maximum, 163%). This value is similar to those reported previously (103% and 106%) (11,12). We have tried to establish a model to describe fetal concentrations by connecting a peripheral or an effect compartment.…”

supporting

confidence: 89%

“…Currently, regimens containing ABC are still recommended as one of the first-line options for adults, including pregnant women (1). ABC pharmacokinetics in adults has been investigated previously (2-9), but only two limited studies (with small numbers of patients, no once-daily administration, and narrow ranges of age and gestational age) were focused on pregnant women (10,11). During pregnancy, some physiological changes can affect the pharmacokinetics of a drug.…”

mentioning

confidence: 99%

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Population Pharmacokinetics of Abacavir in Pregnant Women

Fauchet

Tréluyer

Préta

et al. 2014

Antimicrob Agents Chemother

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e For the first time, a population approach was used to describe abacavir (ABC) pharmacokinetics in HIV-infected pregnant and nonpregnant women. A total of 266 samples from 150 women were obtained. No covariate effect (from age, body weight, pregnancy, or gestational age) on ABC pharmacokinetics was found. Thus, it seems unnecessary to adapt the ABC dosing regimen during pregnancy.A bacavir (ABC) is a potent nucleoside reverse transcriptase inhibitor administered to treat human immunodeficiency virus (HIV) infection and prevent its transmission. Currently, regimens containing ABC are still recommended as one of the first-line options for adults, including pregnant women (1). ABC pharmacokinetics in adults has been investigated previously (2-9), but only two limited studies (with small numbers of patients, no once-daily administration, and narrow ranges of age and gestational age) were focused on pregnant women (10, 11). During pregnancy, some physiological changes can affect the pharmacokinetics of a drug. Therefore, it is important to characterize these changes in a large population in order to use the drug safely and efficiently during pregnancy. Thus, plasma ABC concentrations in nonpregnant and pregnant women were analyzed using a population approach for the first time. The population pharmacokinetics parameters in HIV-infected nonpregnant and pregnant women were estimated, and the final model was used to determine if the current recommended doses produce efficient drug exposure in pregnancy.The HIV-infected pregnant (n ϭ 36) and nonpregnant (n ϭ 114) women had a median age of 35.7 years (range, 15 to 67 years) and a median body weight of 62.5 kg (range, 40 to 102 kg). The median gestational age at pharmacokinetics evaluation was 31 weeks (range, 9 to 41 weeks). A total of 266 samples were obtained from HIV-infected women. Among these samples, 16 were collected in pairs (maternal and cord blood samples). Women received orally an ABC-containing regimen: 300 mg twice daily (47.9%) or 600 mg once daily (52.1%). Blood samples for therapeutic-drug monitoring (TDM) were collected during a visit in the pharmacology unit of Hospital Cochin (Paris, France); therefore, the times elapsed between drug administration and sampling were variable. The pregnant women were enrolled at clinical sites of the ANRS-C01-French Perinatal Cohort (EPF). The mother of the child to be born provided signed informed consent. For the nonpregnant women, ethics committee approval and patient consent are not compulsory in France to use TDM data retrospectively. Plasma ABC concentrations were determined by high-performance liquid chromatography, as previously described (12). The limit of quantification (LOQ) was 0.02 mg/liter. The mean interassay precision for the lowest concentration of the quality controls was 10%. The data were analyzed using Nonmem software (version 6.2), and the first-order conditional estimation with interaction (FOCEI) method was applied (13). The 23 concentrations (8.6%) below the LOQ (BLQ) were replaced by the LOQ/2 ...

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supporting

confidence: 90%

supporting

confidence: 89%

mentioning

confidence: 99%

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Population Pharmacokinetics of Abacavir in Pregnant Women

Fauchet

Tréluyer

Préta

et al. 2014

Antimicrob Agents Chemother

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“…Under steady-state conditions with a dose of 300 mg twice daily, a C max between 1.9 and 2.5 g/ml at 1.0-1.5 h after drug intake was given [17][18][19] . The levels measured in our drug monitoring would be within the reported range, with remarkable interpatient variations ( fig.…”

Section: Discussionmentioning

confidence: 99%

Single-Measurement Therapeutic Drug Monitoring of the HIV/AIDS Drugs Abacavir, Zidovudine, Lamivudine, Efavirenz, Nevirapine, Lopinavir and Nelfinavir

Donnerer

Haas²,

Kessler³

2008

Pharmacology

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Background: There is currently no consensus about the significance of therapeutic drug monitoring (TDM) in the management of human immunodeficiency virus (HIV) infection. Objectives: In this study, single drug levels from routine clinical samples were determined in order to add further data on the therapeutic plasma level range and on drug levels under anti-HIV therapy in general. Materials and Methods: A total of 215 plasma samples obtained from patients with HIV infection for whom TDM was requested for the first time were evaluated. Plasma values were determined for abacavir and zidovudine between 1 and 3 h after drug intake. Lamivudine, efavirenz, nevirapine, lopinavir and nelfinavir plasma values were determined between 1 and 12 h after drug intake. Drug levels were determined with a home-brewed assay based on high-performance liquid chromatography. Results: Plasma concentrations of HIV drugs showed a large variability. Plasma concentrations of abacavir, zidovudine and lamivudine were found to be similar to those reported recently. For efavirenz and nevirapine, 37 and 61% of the samples did not meet the minimum trough levels suggested. For lopinavir and nelfinavir, the majority of the samples (78 and 80%) were found to be within the therapeutic plasma level range. Conclusion: Despite a large variation of anti-HIV drug plasma concentrations, single-measurement TDM may be sufficient in the routine management of the majority of patients.

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“…The pharmacokinetics of most NRTIs (zidovudine [104], stavudine [105], lamivudine [106], abacavir [107]) are not significantly affected by pregnancy and dose adjustment is not required. Renal excretion of didanosine is increased in pregnancy, but dose alteration is probably not required [108].…”

Section: Grading: 1cmentioning

confidence: 99%

11.0 References

2012

HIV Medicine

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Impact of pregnancy on abacavir pharmacokinetics

Abstract: Abacavir AUC during pregnancy was similar to that at 6-12 weeks postpartum and to that for non-pregnant historical controls (5.8 mg.h/l). Consequently, pregnancy does not appear to affect overall abacavir exposure significantly or to necessitate dose adjustments.

Cited by 48 publications

References 16 publications

Population Pharmacokinetics of Abacavir in Pregnant Women

Population Pharmacokinetics of Abacavir in Pregnant Women

Single-Measurement Therapeutic Drug Monitoring of the HIV/AIDS Drugs Abacavir, Zidovudine, Lamivudine, Efavirenz, Nevirapine, Lopinavir and Nelfinavir

11.0 References

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