ArticleAntimicrobial agents and chemotherapy2014
Estimation of intracellular concentration of stavudine triphosphate in HIV-infected children given a reduced dose of 0.5 milligrams per kilogram twice daily.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Physiologically-based pharmacokinetics of ziprasidone in pregnant women.British journal of clinical pharmacology · 2019Article
- Can We Improve Stavudine's Safety Profile in Children? Pharmacokinetics of Intracellular Stavudine Triphosphate with Reduced Dosing.Antimicrobial agents and chemotherapy · 2018Article
- Nucleotide Reverse Transcriptase Inhibitors: A Thorough Review, Present Status and Future Perspective as HIV Therapeutics.Current HIV research · 2017Review
- Effect of reducing the paediatric stavudine dose by half: a physiologically-based pharmacokinetic model.International journal of antimicrobial agents · 2015Article
- Predicting pediatric age-matched weight and body mass index.The AAPS journal · 2014Article
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Authors and funding
5 authors.
Funding
Abstract
The antiviral efficacy of stavudine depends on the trough concentration of its intracellular metabolite, stavudine-triphosphate (d4T-TP), while the degree of stavudine's mitochondrial toxicity depends on its peak concentration. Rates of mitochondrial toxicity are high when stavudine is used at the current standard pediatric dose (1 mg/kg twice daily [BID]). Evidence from adult work suggests that half of the original standard adult dose (i.e., 20 mg BID) may be equally effective, with markedly less mitochondrial toxicity. We present a population pharmacokinetic model to predict intracellular d4T-TP concentrations in pediatric HIV-infected patients administered a dose of 0.5 mg/kg BID. Our model predicted that the reduced pediatric dose would result in a trough intracellular d4T-TP concentration above that of the reduced 20-mg adult dose and a peak concentration below that of the 20-mg adult dose. The simulated pediatric intracellular d4T-TP at 0.5 mg/kg BID resulted in median peak and trough values of approximately 23.9 fmol/10(6) cells (95% prediction interval [PI], 14.2 to 41 fmol/10(6) cells) and 14.8 fmol/10(6) cells (95% PI, 7.2 to 31 fmol/10(6) cells), respectively. The peak and trough concentrations resulting from a 20-mg BID adult dose were 28.4 fmol/10(6) cells (95% PI, 17.3 to 45.5 fmol/10(6) cells) and 13 fmol/10(6) cells (95% PI, 6.8 to 28.6 fmol/10(6) cells), respectively. Halving the current standard pediatric dose should therefore not compromise antiviral efficacy, while markedly reducing mitochondrial toxicity.
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