[Prediction of the pharmacokinetic profiles of doxycycline in humans based on the results of experiments in animals]. / Prognozirovanie farmakokineticheskikh profilei doksitsiklina u cheloveka po rezul'tatam éksperimentov na zhivotnykh.
Antibiot Khimioter
; 33(4): 290-4, 1988 Apr.
Article
em Ru
| MEDLINE
| ID: mdl-3389959
ABSTRACT
Applicability of the "pharmacokinetic time" concept in animal scale-up was evaluated by the findings of the pharmacokinetic study of doxycycline after its bolus intravenous administration to rats in doses of 9 and 18 mg/kg and to cats as 1-hour constant rate infusion in doses of 3.8 and 7.6 mg/kg. Analysis of the pharmacokinetic profiles in the plot of the logarithmic ratio of concentration/dose to "pharmacokinetic time" i. e. time related to body weight raised to the power 0.25 showed that the slopes of the curves for rats, cats and humans (the literature data, intravenous bolus administration in a dose of 2.9 mg/kg) were practically similar. However, no complete coincidence of the curves was observed. When expressed in the "pharmacokinetic time" scale the half lives were equal to 4.6-5.4, 3.5-3.7 and 5.2 h.kg-0.25 respectively. The difference was 1.5-fold while with using the chronological time the difference was about 5-fold (3.1 hours in rats and 15.1 hours in humans). Therefore, with using the "pharmacokinetic time" 10-fold species differences in the total clearance (0.55 and 0.056 l.h-1.kg-1 in rats and humans respectively) transformed into 2-fold differences (0.37 and 0.16 l.h-1.kg-0.75 respectively). Prediction of doxycycline half lives in humans by the experimental findings was successful.
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Base de dados:
MEDLINE
Assunto principal:
Doxiciclina
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
Ru
Ano de publicação:
1988
Tipo de documento:
Article