Evidence for induction of cytochrome P-450I in patients with tropical chronic pancreatitis

Theophylline kinetics, as an in vivo probe for the potentially toxic cytochrome P-450I pathway of drug metabolism, were studied in 11 healthy volunteers and 11 patients with calcific chronic pancreatitis at Madras, South India. Theophylline clearance was faster in the patients than controls [median...

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Published inInternational journal of clinical pharmacology, therapy, and toxicology Vol. 28; no. 6; p. 235
Main Authors Chaloner, C, Sandle, L N, Mohan, V, Snehalatha, C, Viswanathan, M, Braganza, J M
Format Journal Article
LanguageEnglish
Published Germany 01.06.1990
Subjects
Adolescent
Adult
Chronic Disease
Cytochrome P-450 Enzyme System - biosynthesis
Enzyme Induction
Female
Humans
Male
Metabolic Clearance Rate
Middle Aged
Pancreatitis - enzymology
Theophylline - pharmacokinetics
Tropical Climate
Xenobiotics - metabolism
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Summary:Theophylline kinetics, as an in vivo probe for the potentially toxic cytochrome P-450I pathway of drug metabolism, were studied in 11 healthy volunteers and 11 patients with calcific chronic pancreatitis at Madras, South India. Theophylline clearance was faster in the patients than controls [median 69 (range 39-114) vs 45 (33-56) ml h-1 kg-1, p = 0.003]. In keeping with this finding, detailed social histories identified a higher exposure level in the patients to xenobiotics that are inducers of cytochrome P-450I and/or yield reactive metabolites upon processing thereby (score 7, 4-11 vs 3, 2-9, p = 0.002). However, the concentration of D-glucaric acid in urine, as a marker of phase II conjugating pathways of drug metabolism, was similar in patients and controls. This pattern of drug metabolism could predispose to oxidant stress: hence micronutrient antioxidant supplements may have therapeutic (or even prophylactic) value in tropical chronic pancreatitis.
ISSN:0174-4879