Pharmacokinetics of theophylline in the newborn and adult rabbit

In vivo and isolated perfused liver approaches

A. Bortolotti, M. Corada, M. M. Barzago, A. Celardo, A. Guaitani, M. Bonati

Research output: Contribution to journalArticle

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Abstract

The isolated perfused liver technique is the in vitro system most nearly comparable to the intact liver for experimental investigations on drug metabolism. The model currently used employs liver from different species, but only adults. For the first time, we have set up an experimental investigation involving perfusion of the liver of newborn animals. Using theophylline (TH) as tool drug, an in vivo/in vitro and adult/newborn disposition study was made in the rabbit. After a 10 mg/kg dose iv to adult rabbits and ip to rabbits at birth, the pharmacokinetic profile of TH was analyzed during liver perfusion at comparable TH concentrations in the medium. A few biochemical variables were recorded. No age-related differences were observed in the release of glutamic-oxalacetic transaminase and lactate dehydrogenase over the perfusion time. O2 consumption was higher in adults than in newborns, in accordance with the lower metabolic capacity of the neonatal liver, supported by the lower values of cytochrome P-450, cytochrome c, and glutathione. In vivo and in vitro values were close in adults and newborns for half-life (average 5.2 vs. 5.4 and 27 vs. 35 hr, respectively) and intrinsic clearance of TH (13 vs. 11 and 0.032 vs. 0.021 ml/min). The qualitative and quantitative TH metabolic patterns in the medium and in vivo also were close in adult animals. Only unchanged TH was detected in newborn perfusate. The isolated perfused liver technique appears to offer a reliable model for studying the in vitro ontogeny of drug metabolism, and for making in vitro and in vivo physiological and pharmacological comparisons.

Original languageEnglish
Pages (from-to)430-435
Number of pages6
JournalDrug Metabolism and Disposition
Volume19
Issue number2
Publication statusPublished - 1991

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Pharmacokinetics
Theophylline
Liver
Rabbits
Perfusion
Metabolism
Animals
Pharmaceutical Preparations
Newborn Animals
Transaminases
Cytochromes c
L-Lactate Dehydrogenase
Cytochrome P-450 Enzyme System
Glutathione
Half-Life
In Vitro Techniques
Parturition
Pharmacology

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Pharmacokinetics of theophylline in the newborn and adult rabbit : In vivo and isolated perfused liver approaches. / Bortolotti, A.; Corada, M.; Barzago, M. M.; Celardo, A.; Guaitani, A.; Bonati, M.

In: Drug Metabolism and Disposition, Vol. 19, No. 2, 1991, p. 430-435.

Research output: Contribution to journalArticle

Bortolotti, A. ; Corada, M. ; Barzago, M. M. ; Celardo, A. ; Guaitani, A. ; Bonati, M. / Pharmacokinetics of theophylline in the newborn and adult rabbit : In vivo and isolated perfused liver approaches. In: Drug Metabolism and Disposition. 1991 ; Vol. 19, No. 2. pp. 430-435.
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