Antiretroviral pharmacokinetic profile: A review of sex differences

Ofotokun, Ighovwerha; Chuck, Susan K.; Hitti, Jane

doi:10.1016/s1550-8579(07)80025-8

Cited by 94 publications

(66 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the basis of LPV/r (tablet) pharmacokinetic data from a study of Boffito et al (6a) performed in 16 (6 female) HIV-negative healthy volunteers, LPV postpartum pharmacokinetics in the current study were comparable to those of nonpregnant adults and may therefore provide a more reasonable estimation of reduced LPV exposure during pregnancy. Comparison of these data is justified since there are no reported differences in LPV pharmacokinetics between healthy volunteers and HIV-infected subjects (9) or any known gender-related differences in LPV pharmacokinetics (27).…”

Section: Discussionmentioning

confidence: 99%

Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

Else

Douglas

Dickinson

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Lopinavir exposure was reduced during the third trimester in pregnant women receiving standard dosing of the soft-gel capsule (SGC; 400/100 mg twice daily [b.i.d.]). Pharmacokinetic data on the lopinavir tablet in pregnancy are limited. On the basis of the tablet's improved bioavailability, standard dosing (400/100 mg b.i.d.) may provide adequate lopinavir exposure in pregnancy without a need for dose adjustment. Here we compared the total and unbound lopinavir pharmacokinetics throughout pregnancy in the second and third trimesters in HIV-infected women receiving standard dosing of the lopinavir SGC or tablet. Postpartum sampling was also performed in patients continuing therapy postdelivery. Blood samples were collected at 0 to 12 h postdosing, and lopinavir concentrations were determined by high-pressure liquid chromatography-tandem mass spectrometry. Nineteen patients were included: 8 received the SGC (cohort 1) and 11 received the tablet (cohort 2). Total lopinavir exposures in the third trimester were lower than those in the second trimester (35 and 28% for cohorts 1 and 2, respectively) and postpartum (35% for cohort 2). In the third trimester, the area under the concentration-time curve (AUC) from 0 to 12 h (AUC 0 -12 ) and maximum concentration were ϳ15% and 25% higher, respectively, for the lopinavir tablet than the SGC. One SGC patient had lopinavir concentrations of <1,000 ng/ml; all patients on the tablet had concentrations of >1,000 ng/ml. In cohort 2, the percentage of the AUC that was unbound was higher (nonsignificantly) in the second (1.28%) and third (1.18%) trimesters than postpartum (1.01%). Seventeen of 19 patients had an undetectable viral load at delivery. There were no HIV transmissions. Although lopinavir (tablet) exposures were reduced during the third trimester, the higher total and unbound concentrations achieved in women receiving the tablet than in women receiving the SGC suggest that the tablet's improved oral bioavailability may partly compensate for the reduction in lopinavir exposure during the later stages of pregnancy.A ntiretroviral therapies (ARTs), with the exception of zidovudine, are unlicensed for use in pregnancy. However, they are widely used, in accordance with national and international guidelines, both for maternal treatment and for the prevention of HIV mother-to-child transmission (MTCT). Multiple physiological changes which can impact the pharmacokinetics (PKs) of these agents occur during pregnancy; therefore, studies in pregnancy are required to ensure appropriate dosing and avoid unnecessary toxicity or treatment failure. Protease inhibitors (PIs) are widely used during pregnancy for both treatment and prevention of MTCT due to their efficacy, lack of CD4 count-dependent toxicity, and short half-lives (t 1/2 s). However, plasma concentrations of certain protease inhibitors have repeatedly been shown to be significantly reduced during the third trimester, with some concerns over efficacy (37).Lopinavir (LPV)-ritonavir (RTV), or LPV/r, is used during pregnancy,...

show abstract

Section: Discussionmentioning

confidence: 99%

Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

Else

Douglas

Dickinson

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…However, few studies have investigated the pharmacokinetics differences between women and men (6)(7)(8) and in pregnant women (9). Studies conducted with a small number of participants suggest that protease inhibitor (PI) levels in plasma are higher in women (10)(11)(12), although PI exposure decreases during pregnancy, especially in the third trimester (13).…”

mentioning

confidence: 99%

Randomized Clinical Trial Comparing the Pharmacokinetics of Standard- and Increased-Dosage Lopinavir-Ritonavir Coformulation Tablets in HIV-Positive Pregnant Women

Santini-Oliveira

Estrela

Veloso

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 g/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 g/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard-and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.)

show abstract

“…In this study, women gender has been shown to be related with increased rate of treatment interruptions (Adjusted OR = 1.91; 95% CI = 1.1-3.4), mainly because of poor tolerance. This gender issue has previously been studied in a small pharmacokinetic study 47 which showed that ATV concentrations were higher in women than in men. Gender driven differences in drug concentrations may be due to different pharmacokinetic parameters such as bioavailability, distribution, or metabolism.…”

Section: Treatment-experienced Patients With Detectable Viral Loadmentioning

confidence: 99%

Pharmacotherapy of HIV: A Focus on Atazanavir/Ritonavir a Potent and Convenient Once Daily Ritonavir Boosted Protease-Inhibitor for HIV-1 Infected Adults

Allavena¹,

Trancart

2009

Clinical Medicine. Therapeutics

View full text Add to dashboard Cite

Atazanavir is the fi rst azapeptide protease inhibitor. As a consequence of metabolism by the Cytochrome P450 system and excretion by drug-transporters such as P-Glycoprotein, drug interactions are considerable. They can be used to improve effi cacy (ritonavir boosting) but may also cause adverse effects. Effi cacy of ATV/RTV has been shown to be comparable to lopinavir/ritonavir in antiretroviral naïve patients, providing even better results in patients with high viral load. Effi cacy has also been demonstrated in maintenance therapy in antiretroviral-experienced patients, and in patients with previous virologic failure, providing the best virologic response when the virus harbors less than four resistance PI mutations. The gastrointestinal tolerability and the lipid profi le are better than with other PIs. The major side effect is a jaundice caused by unconjugated hyperbilirubinemia that rarely leads to discontinuation. ATV/RTV simple administration as well as tolerability may be linked with better treatment adherence. ATV/RTV is simple, potent and well tolerated. Thus it takes an important place in the treatment of HIV-infected patients, preferentially in antiretroviral-naïve or moderately pretreated populations.

show abstract

Antiretroviral pharmacokinetic profile: A review of sex differences

Cited by 94 publications

References 30 publications

Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

Improved Oral Bioavailability of Lopinavir in Melt-Extruded Tablet Formulation Reduces Impact of Third Trimester on Lopinavir Plasma Concentrations

Randomized Clinical Trial Comparing the Pharmacokinetics of Standard- and Increased-Dosage Lopinavir-Ritonavir Coformulation Tablets in HIV-Positive Pregnant Women

Pharmacotherapy of HIV: A Focus on Atazanavir/Ritonavir a Potent and Convenient Once Daily Ritonavir Boosted Protease-Inhibitor for HIV-1 Infected Adults

Contact Info

Product

Resources

About