Summary
The pharmacokinetics of oral zidovudine in HIV-infected children and adults are reported. Fourty-six patients were investigated. For data analysis three groups of similar size were formed: young children 4 months −4 years, n=15 (group 1), older children up to 13 years, n=16 (group 2) and young adults, n=15 (group 3). After a single oral dose repeated blood samples were taken 1/2 hourly during a period of 4 hours and zidovudine concentrations in plasma were determined by high performance liquid chromatography. For better comparison of dose dependent parameters peak concentrations (Cmax) and the area under the time-concentration curves (AUC) were normalized either to the dose/body weight (bw) or the dose/body surface area (bs), respectively. Time to reach peak concentrations and mean terminal elimination half-life times (t1/2β=63.4±47.6, 74.9±54.9 and 56.9±16.4 min in group 1, 2 and 3, respectively, mean ± SD) were not significantly different between the three groups. With normalization to dose/bw young children in comparison to adults had significantly lower Cmax (2.7±1.3 vs. 4.6±2.4 µmol/l, p=0.016) and AUC (226±108 vs. 373±224 µmol·min/l, p=0.038). Group 2 gave intermediate values. However, with normalization to dose/bs differences in Cmax (6.5±3.3, 7.3±4.2 and 6.8±3.6 µmol/l, in group 1, 2, and 3, respectively) and AUC (563±313, 691±351 and 555±342 µmol·min/l, in group 1, 2 and 3) were not significant between the three groups. It is likely that changes in body water content with age may account for most of these differences observed. In conclusion, a similar pharmacokinetic profile was found in children older than 3 months as compared to older children or adults.
Zusammenfassung
In dieser Studie wurden die Pharmakokinetik von oral appliziertem Zidovudin bei 46 HIV-infizierten Kindern und Erwachsenen untersucht. Zur Auswertung wurden die Patienten in drei Altersgruppen gleicher Größe eingeteilt: Kinder von 4 Monaten bis 4 Jahre (Gruppe 1, n=15), Kinder von 4 bis 13 Jahren (Grupp 2, n=16) und junge Erwachsene (Gruppe 3, n=15). Nach Einnahme einer oralen Einzeldosis wurde halbstündlich über 4 Stunden Blut entnommen. Die Zidovudin-Konzentrationen im Plasma wurden mittels Hochdruckflüssigkeits-Chromatographie bestimmt. Zur besseren Vergleichbarkeit von dosisabhängigen Parametern wurde die Maximalkonzentration (Cmax) und die Fläche unter der Zeit-Konzentrationskurve (AUC) auf die Dosis/Körpergewicht bzw. Dosis/Körperoberfläche normalisiert. Die Zeit bis zum Erreichen von Cmax und die Eliminationshalbwertszeit (t1/2β=63.4±47.6, 74.9±54.9 und 56.9±16.4 min in Gruppe 1, 2 und 3, Mittelwert±Standardabweichung) waren nicht signifikant zwischen den drei Gruppen verschieden. Nach Normalisierung auf Dosis/Körpergewicht wiesen Kinder in Gruppe 1 im Vergleich zu Gruppe 3 signifikant niedrigere Werte für die Cmax (2.7±1.3 vs. 4.6±2.4 µmol/l, p=0.016) und die AUC (226±108 vs 373±224 µmol·min/l, p=0.038) auf. Die Mittelwerte für Cmax und AUC für die Gruppe 2 lagen zwischen den für Gruppe 1 und 3 gemessenen Werten. Nach Normalisierung auf Dosis/Körperoberfläche hingegen, waren die Unterschiede zwischen den drei Gruppen nicht signifikant (Cmax: 6.5±3.3, 7.3±4.2 und 6.8±3.6 µmol/l; AUC: 563±313, 691±351 und 555±342 µmol·min/l, jeweils in Gruppe, 1, 2 und 3). Es ist daher naheliegend, daß altersbedingte Veränderungen im Körperwasseranteil für die beobachteten Unterschiede zumindest teilweise verantwortlich sind. Zusammenfassend läßt sich sagen, daß die Pharmakokinetik von Zidovudin für Kinder älter als 3 Monate nicht altersabhängig zu sein scheint.
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Wintergerst, U., Rolinski, B., Notheis, G. et al. Pharmacokinetics of orally administered zidovudine in HIV-infected children and adults. Infection 23, 344–348 (1995). https://doi.org/10.1007/BF01713563
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DOI: https://doi.org/10.1007/BF01713563