TITLE

Pharmacokinetics of Antiretroviral Drug Varies With Formulation in the Target Population of Children With HIV-1

AUTHOR(S)
Kasirye, P; Kendall, L; Adkison, K K; Tumusiime, C; Ssenyonga, M; Bakeera-Kitaka, S; Nahirya-Ntege, P; Mhute, T; Kekitiinwa, A; Snowden, W; Burger, D M; Gibb, D M; Walker, A S
PUB. DATE
February 2012
SOURCE
Clinical Pharmacology & Therapeutics;Feb2012, Vol. 91 Issue 2, p272
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The bioequivalence of formulations is usually evaluated in healthy adult volunteers. In our study in 19 HIV-1-infected Ugandan children (1.8-4 years of age, weight 12 to <15 kg) receiving zidovudine, lamivudine, and abacavir solutions twice a day for ≥24 weeks, the use of scored tablets allowed comparison of plasma pharmacokinetics of oral solutions vs. tablets. Samples were collected 0, 1, 2, 4, 6, 8, and 12 h after each child's last morning dose of oral solution before changing to scored tablets of Combivir (coformulated zidovudine + lamivudine) and abacavir; this was repeated 4 weeks later. Dose-normalized area under curve (AUC)0-12 and peak concentration (Cmax) for the tablet formulation were bioequivalent with those of the oral solution with respect to zidovudine and abacavir (e.g., dose-normalized geometric mean ratio (dnGMR) (tablet:solution) for zidovudine and abacavir AUC0-12 were 1.01 (90% confidence interval (CI) 0.87-1.18) and 0.96 (0.83-1.12), respectively). However, lamivudine exposure was ~55% higher with the tablet formulation (AUC0-12 dnGMR = 1.58 (1.37-1.81), Cmax dnGMR = 1.55 (1.33-1.81)). Although the clinical relevance of this finding is unclear, it highlights the impact of the formulation and the importance of conducting bioequivalence studies in target pediatric populations.
ACCESSION #
70478707

 

Related Articles

  • A 4-month-old in respiratory distress. MULLAN, PAUL; STEENHOFF, ANDREW; RUTSTEIN, RICHARD // Contemporary Pediatrics;Oct2009, Vol. 26 Issue 10, p26 

    The article describes the case of a 4-month-old infant girl who was diagnosed with HIV. The patient experienced various symptoms, including cough, rapid breathing, jaundice and white stools. The infant was subjected to highly active antiretroviral therapy (HAART) with zidovudine,...

  • Cardiometabolic risk factors among HIV patients on antiretroviral therapy. Kiage, James N.; Heimburger, Douglas C.; Nyirenda, Christopher K.; Wellons, Melissa F.; Bagchi, Shashwatee; Chi, Benjamin H.; Koethe, John R.; Arnett, Donna K.; Kabagambe, Edmond K. // Lipids in Health & Disease;2013, Vol. 12 Issue 1, p1 

    Background: HIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk. Methods: Adult patients (n=118) in Lusaka, Zambia were recruited at the time of...

  • Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda. Goodall, R. L.; Dunn, D. T.; Pattery, T.; van Cauwenberge, A.; Nkurunziza, P.; Awio, P.; Ndembi, N.; Munderi, P.; Kityo, C.; Gilks, C. F.; Kaleebu, P.; Pillay, D. // Journal of Antimicrobial Chemotherapy (JAC);Jul2014, Vol. 69 Issue 7, p1938 

    Objectives We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring. Methods NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART)...

  • Long-Term Immunovirogical Effect and Tolerability of a Maraviroc-Containing Regimen in Routine Clinical Practice. Genebat, Miguel; Ruiz-Mateos, Ezequiel; Pulido, Ildefonso; González-Serna, Alejandro; García-Pergañeda, Antonio; Méndez, Gema; Romero-Sánchez, María Concepción; Ferrando-Martínez, Sara; Leal, Manuel // Current HIV Research;Sep2010, Vol. 8 Issue 6, p482 

    Objectives: to analyze the long-term immunovirological effect and tolerability of a maraviroc-containing antiretroviral therapy in viraemic and pretreated HIV-infected patients with a high prevalence of hepatitis C virus (HCV) coinfection. Methods: forty-six R5 HIV-infected patients (48%...

  • Maraviroc versus Efavirenz, Both in Combination with Zidovudine-Lamivudine, for the Treatment of Antiretroviral-Naive Subjects with CCR5-Tropic HIV-1 Infection. Cooper, David A.; Heera, Jayvant; Goodrich, James; Tawadrous, Margaret; Saag, Michael; DeJesus, Edwin; Clumeck, Nathan; Walmsley, Sharon; Ting, Naitee; Coakley, Eoin; Reeves, Jacqueline D.; Reyes-Teran, Gustavo; Westby, Mike; Van Der Ryst, Elna; Ive, Prudence; Mohapi, Lerato; Mingrone, Horacio; Horban, Andrzej; Hackman, Frances; Sullivan, John // Journal of Infectious Diseases;3/15/2010, Vol. 201 Issue 6, p803 

    Background. The MERIT (Maraviroc versus Efavirenz in Treatment-Naive Patients) study compared maraviroc and efavirenz, both with zidovudine-lamivudine, in antiretroviral-naive patients with R5 human immunodeficiency virus type 1 (HIV-1) infection. Methods. Patients screened for R5 HIV-1 were...

  • Pharmacokinetic optimisation of the treatment of cancer with high dose zidovudine. Danesi, R.; Falcone, A.; Conte, P.F.; Tacca, M.D.; Del Tacca, M // Clinical Pharmacokinetics;1998, Vol. 34 Issue 2, p173 

    The thymidine analogue zidovudine is currently used for the treatment of HIV-infected patients, as the early development of the drug as an anticancer agent yielded modest results. A comprehensive preclinical analysis, however, showed that inhibitors of de novo thymidylate synthesis, including...

  • Evaluation of Saliva as an Alternative Matrix for Monitoring Plasma Zidovudine, Lamivudine and Nevirapine Concentrations in Rwanda. Gras, Alain; Schneider, Serge; Karasi, Jean-Claude; Ternes, Anne-Marie; Sauvageot, Nicolas; Karasi-Omes, Christine; Henry, Anne-Pascale; Schmit, Jean-Claude; Seguin-Devaux, Carole; Arendt, Vic // Current HIV Research;Jun2011, Vol. 9 Issue 4, p223 

    Saliva may provide interesting advantages as matrix for compliance measurements, pharmacokinetic studies and therapeutic drug monitoring in resource limited countries. We investigated the feasibility of using saliva for compliance monitoring of zidovudine (ZDV), lamivudine (3TC) and nevirapine...

  • Phannacokinetics of lamivudine & stavudine in generic fixed-dose combinations in HIV-1 infected adults in India. Kumar, A. K. Hemanth; Ramachandran, Geetha; Rajasekaran, S.; Padmapriyadarsini, C.; Narendran, G.; Subramanyam, S. Anitha Sudha; Kumaraswami, V.; Swaminathan, Soumya // Indian Journal of Medical Research;Oct2009, Vol. 130 Issue 4, p451 

    Background & objectives: Antiretroviral drug concentrations are important determinants of clinical response to a drug accounting for both toxicity and efficacy. Several factors such as age, ethnicity, body weight and patients' immune status may influence antiretroviral drug concentrations. The...

  • Antiretrovirals.  // Reactions Weekly;5/10/2008, Issue 1201, p8 

    The article describes the case of eighteen patients in the ASCENT study or EPIC study with HIV infection developed hepatotoxicity during treatment with antiretrovirals. Patients in the ASCENT study were receiving aplaviroc, zidovudine and lamivudine twice daily and those in the EPIC study were...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics