Oxidative drug metabolism and inducibility by phenobarbital in sickle cell anemia

Karl Anderson, C. M. Peterson, A. P. Alvares, A. Kappas

Research output: Contribution to journalArticle

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Abstract

The plasma elimination rates of antipyrine and phenylbutazone were studied in 8 patients with sickle cell anemia. The mean antipyrine half-life (t 1 2) in plasma was not significantly different in the sickle cell patients (12.0 ± 3.0 hr) than in a control group of 20 normal subjects (12.7 ± 0.9 hr). For phenylbutazone the mean t 1 2 was shorter in the sickle cell patients (2.1 ± 0.1 days) than in normal subjects (3.3 ± 0.2 days, p < 0.001); both mean apparent volume of distribution (aVD) and mean metabolic clearance rate (MCR) for this drug were significantly higher in the sickle cell group, which suggests increased extravascular distribution as well as more rapid hepatic metabolism. After administration of phenobarbital (2 to 3 mg/kg daily for 2 wk) consistent increases in rates of antipyrine and phenylbutazone metabolism were observed in 6 sickle cell anemia patients, which wr0e comparable to those observed in 5 normal subjects. Two other patients who were taking drugs (methyltestosterone, isoniazid) known to alter cytochrome P-450 function did not respond typically. Our results suggest that cytochrome P-450 function and sensitivity to phenobarbital induction are unimpaired in most sickle cell anemia patients. Since uptake of heme into hepatocytes is probably increased in this disorder, this suggests that an adapative response develops during long-term hemolysis such that heme biosynthesis and formation of microsomal cytochromes are not repressed.

Original languageEnglish (US)
Pages (from-to)580-587
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume22
Issue number5 PART 1
StatePublished - Nov 1977
Externally publishedYes

Fingerprint

Sickle Cell Anemia
Phenobarbital
Antipyrine
Phenylbutazone
Pharmaceutical Preparations
Heme
Cytochrome P-450 Enzyme System
Methyltestosterone
Metabolic Clearance Rate
Isoniazid
Cytochromes
Hemolysis
Half-Life
Hepatocytes
Control Groups
Liver

ASJC Scopus subject areas

  • Pharmacology

Cite this

Oxidative drug metabolism and inducibility by phenobarbital in sickle cell anemia. / Anderson, Karl; Peterson, C. M.; Alvares, A. P.; Kappas, A.

In: Clinical Pharmacology and Therapeutics, Vol. 22, No. 5 PART 1, 11.1977, p. 580-587.

Research output: Contribution to journalArticle

Anderson, K, Peterson, CM, Alvares, AP & Kappas, A 1977, 'Oxidative drug metabolism and inducibility by phenobarbital in sickle cell anemia', Clinical Pharmacology and Therapeutics, vol. 22, no. 5 PART 1, pp. 580-587.
Anderson, Karl ; Peterson, C. M. ; Alvares, A. P. ; Kappas, A. / Oxidative drug metabolism and inducibility by phenobarbital in sickle cell anemia. In: Clinical Pharmacology and Therapeutics. 1977 ; Vol. 22, No. 5 PART 1. pp. 580-587.
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