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Selective effects of somatostatin analogs on human drug‐metabolizing enzymes
Author(s) -
Rasmussen Eva,
Eriksson Barbro,
Öberg Kjell,
Bondesson Ulf,
Rane Anders
Publication year - 1998
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(98)90148-5
Subject(s) - glucuronidation , somatostatin , glucuronosyltransferase , pharmacology , codeine , chemistry , cyp3a4 , lanreotide , medicine , endocrinology , drug , hormone , enzyme , cytochrome p450 , morphine , growth hormone , biochemistry , acromegaly , microsome
Pharmacologic or surgical manipulation with growth hormone secretion or with the physiologic release of somatostatin and growth hormone‐releasing hormone affects some rat liver enzymes, especially the sex‐differentiated ones. We investigated the effects of two somatostatin analogs on several enzyme functions in six patients with carcinoid syndrome, using codeine as a probe drug. Codeine was given intravenously and its N ‐ and O ‐demethylation, as well as 6‐glucuronidation catalyzed by CYP3A, CYP2D6, and uridine diphosphate‐glucuronosyltransferase, respectively, were studied before and during treatment with somatostatins. After 3 days of treatment with somatostatins the partial metabolic clearance of codeine by N ‐demethylation decreased by 21% to 64% in all patients (mean change, 44%; p < 0.05), and the clearance by O ‐demethylation was decreased by 20% to 69% in five of the patients (mean change in all patients, 35%; p < 0.05). In contrast, the partial clearance by 6‐glucuronidation and the total systemic clearance of codeine were unchanged. Our results may be caused by the inhibition of growth hormone secretion induced by the somatostatins, inasmuch as direct metabolic interactions with these peptide drugs are improbable. The decline in CYP3A4 and CYP2D6 activity might have clinical implications when substrates of these enzymes with low therapeutic indices are combined with somatostatin analogs. Because the formation of morphine from codeine was altered, the analgesic effect of this drug may be reduced during concomitant treatment with somatostatins. Clinical Pharmacology & Therapeutics (1998) 64 , 150–159; doi: