title: Evidence for induction of cytochrome P-450I in patients with tropical chronic pancreatitis.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Royal Infirmary, Manchester, UK.
authors.forename: C
authors.initials: C
authors.lastname: Chaloner
authors.forename: L N
authors.initials: LN
authors.lastname: Sandle
authors.forename: V
authors.initials: V
authors.lastname: Mohan
authors.forename: C
authors.initials: C
authors.lastname: Snehalatha
authors.forename: M
authors.initials: M
authors.lastname: Viswanathan
authors.forename: J M
authors.initials: JM
authors.lastname: Braganza
mesh_terms: D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010195:Pancreatitis / Q000201:enzymology*; D013806:Theophylline / Q000493:pharmacokinetics; D014329:Tropical Climate; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline