¹Departments of Neurology, Biochemistry, and Pharmacology, National Cheng Kung University, Medical College, Tainan, Taiwan, and the School of Pharmacy, University of California, San Francisco, Calif, USA.

Correspondence: Jin-ding Huang, PhD, Department of Pharmacology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan.

^*Supported by grants NSC82-0412-B006-17 from the National Sciences Council of the Republic of China (Taipei, Taiwan) and DOH83-TD-081 from the Department of Health of the Republic of China (Taipei, Taiwan).

Received 7 December 1994; Accepted 20 April 1995.

Abstract

Propranolol pharmacokinetics among different genotypes of CYP2D6 was compared in this study. The Chinese (Han) population consisted of 44 healthy unrelated individuals living in southern Taiwan. Endonuclease tests based on polymerase chain reaction were used to determine C/T₁₈₈ genotypes of CYP2D6 in leukocyte deoxyribonucleic acid. Based on codon 188 genotypes, subjects were categorized into three groups: homozygous C/C₁₈₈ (n = 13), heterozygous C/T₁₈₈ (n = 14); and homozygous T/T₁₈₈ (n = 17). Each subject was given a 40 mg propranolol tablet. Blood samples were drawn before and 12 hours after propranolol administration to measure propranolol and 4-hydroxypropranolol. Three genotypes showed distinct time profiles of plasma propranolol and 4-hydroxypropranolol. The area under plasma concentration curve values (mean SEM), were 322.0 40.8, 481.6 77.5, and 766.1 92.8 nmol hr/L, respectively, for C/C₁₈₈, C/T₁₈₈, and T/T₁₈₈ subjects (p < 0.05). The 48-hour excreted amount of 4-hydroxy-S-propranolol-O-glucuronide, but not 4-hydroxy-R-propranolol-O-glucuronide, was significantly higher for C/C₁₈₈ than for T/T₁₈₈ subjects (p < 0.05). This study shows a different propranolol disposition in Chinese subjects of different CYP2D6 genotypes.