Asian Americans

Desipramine

Mean total clearance of desipramine from plasma was significantly lower in Chinese (73.5 +/- 38.8 1/h) than in U.S. Caucasians (123 +/- 57 l/h),P < 0.05. (Measured after 5 days of 100 mg oral admission). 29% of the Chinese and 0% of the U.S. Caucasians demonstrated slow clearance (< 33 1/h) suggesting that a considarable percentage of Chinese would be at risk for toxicity with routine doses. Area Under the Curve was significantly higher among Chinese (946 ng/ml h) compared to the US Caucasians (654 ng/ml h).

Healthy volunteers: 14 Chinese and 16 U.S. Caucasians
(Chinese: mean time in US was 4.2 years; 1 born in US; 10 were natives of China, 3 of Taiwan and one of Hong Kong).

(Rudorfer et al., 1984)

Diazepam

Desmethyldiazepam levels were higher in Orientals than Caucasians. The free fraction of diazepam was identical in both groups (0.02). Volume of distribution at steady state (Vdss) was different when calculated as absolute volume Vdss = 76.55 (+/- 9.63) in Caucasians and 54.96 (+/- 4.55) in Asian Americans (p = 0.04) and marginally significant when corrected for body weight Vdssl/kg = 1.10 (+/- 0.11) in Caucasian and 0.88 (+/- 0.05) in Asian Americans, (p = 0.07). Total body clearance, but not elimination half-life, was higher in Caucasians compared to Asian Americans.

(N = 25; Caucasians (n=12) and Orientals (Asian Americans, n=13)), Ghoneim, 1981.

Pharmacokinetics Asian Americans (USA)

Toxicity

Liberation

Administration/absorption

Distribution

Diazepam Asian Americans: The free fraction of diazepam was identical in both races (0.02). Desmethyldiazepam levels were higher in Asian Americans than Caucasians. Volume of distribution at steady state (Vdss) was different when calculated as absolute volume Vdss = 76.55 (+/- 9.63) in Caucasians and 54.96 (+/- 4.55) in Asian Americans (p = 0.04) and marginally significant when corrected for body weight Vdssl/kg = 1.10 (+/- 0.11) in Caucasian and 0.88 (+/- 0.05) in Asian Americans, (p = 0.07)(Ghoneim, 1981).

Metabolism

CYP1A2

CYP3A

CYP2B6

CYP2C8

CYP2C9

CYP2C19

CYP2D6

Excretion

Diazepam: Total body clearance (Cl), but not elimination half-life (t 1/2), was higher in Caucasians (t 1/2 = 37.70 (+/- 5.53 hr)) compared to Asian Americans (t1/2 = 41.77 (+/- 3.80)).(Ghoneim, 1981).

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