Influence of ORM1 polymorphism on serum concentration of free nortriptyline.
- Author:
Che ZHANG
1
;
Zi-Liang TU
;
Qi-Bin WANG
;
Xiao-Li CHENG
;
Peng-Hua ZHANG
Author Information
1. Yueyang Medical College, Shiyan 442000, China.
- Publication Type:Journal Article
- MeSH:
Adult;
Area Under Curve;
Genotype;
Humans;
Male;
Nortriptyline;
analogs & derivatives;
blood;
pharmacokinetics;
Orosomucoid;
genetics;
metabolism;
Polymorphism, Genetic;
Protein Binding
- From:
Acta Pharmaceutica Sinica
2007;42(8):843-848
- CountryChina
- Language:Chinese
-
Abstract:
To study the effect of alpha1-acid glycoprotein 1 (ORM1) polymorphism on the concentration of free nortriptyline in serum, genotyping analysis was employed in ORM1 by sequencing. Eighteen unrelated male adults were chosen and given a single dose of 25 mg nortriptyline orally, then the blood samples were taken at 0, 1, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96 and 168 hours after drug administration. Nortriptyline and 10-OH-nortriptyline in serum and ultrafiltrate were detected for the total and free concentration by using HPLC-MS/MS. Pharmacokinetic parameters were compared among different ORM1 genotypes. No significant differences were shown in the pharmacokinetic parameters of total nortriptyline and 10-OH-nortriptyline. The mean AUC(0-infinity) of free nortritpyline in ORM1 * F/ * F1 subjects was significantly higher than that in ORM1 * F1/ * S and ORM1 * S/ * S subjects [(119.1 +/- 74.4) ng x mL(-1) x h vs (51.4 +/- 23.2) ng x mL(-1) x h and (42.4 +/- 11.6) ng x mL(-1) x h]. The percentage of protein binding in subjects with ORM1 * F1/ * F1 genotype at 2, 3, 4, 6, 8 and 12 h after administration was slightly lower than in those with ORM1 * F1/ * S and ORM1 * S/ * S genotypes while the distinct difference was shown at 4 h (P < 0.05). Different ORM1 genotypes might affect the protein binding percentage and the concentration of serum free nortriptyline. The ability binding to the drug was higher in subjects with ORM1 * S/ * S genotype than in those with other two genotypes, so as to cause the lower concentration of free nortriptyline.
