Write an essay about cases of CYP2D6 genotypes affecting codeine pharmacokinetics.

 Polymorphism exists in the cytochrome P450 (CYP450) metabolizing enzymes and that lead to a difference in the metabolic processes in each individual. Codeine is metabolized by CYP2D6 and converted to morphine and other metabolites that are responsible for its pharmacological action. Due to the polymorphism in CYP2D6 based on different alleles, peoples have different metabolic pharmacokinetic classified as extensive metabolizer (EM), poor metabolizers (PM). Yue, Q. Y., et al. (1991) studied the pharmacokinetic after an oral administration of 50 mg codeine phosphate in eight extensive (EM) and six poor (PM) Caucasians hydroxylators of debrisoquine. The pharmacokinetics parameters were analyzed of codeine and its metabolites i.e. norcodeine (NC), codeine-6-glucuronide (C6G), NC-glucuronide (NCG), morphine (M), normorphine (NM), M-3 (M3G) and 6-glucuronides (M6G). The pharmacokinetic parameters for codeine were as follows Cmax (EM; 292± 95 nmol/L; PM: 282± 150 nmol/L), AUC (EM: 1010 ± 391 nmol; PM: 1020 ± 340 nmol), t1/2 (EM: 2.43 ±0.58 h; PM: 2.90+0.41 h) and CL (EM: 2.10 ±0.84 l/h kg; PM: 1.92+0.63 l/h kg) which did not significantly different in these groups. But there is a significant difference in the kinetic of metabolites of codeine in EM and PM.