The effect of urine pH on debrisoquine phenotyping: application of an HPLC-method.
The effect of urine pH on debrisoquine metabolic ratio (MR) was studied in 6 healthy volunteers. They were phenotyped on two separate occasions, firstly when urine was made alkaline with orally given sodium bicarbonate, and secondly when urine was acidified with oral ammonium chloride. The concentrations of debrisoquine and 4-hydroxydebrisoquine were analyzed by an HPLC (high performance liquid chromatographic) method, which was compared with a standard GC (gas chromatographic) method. The calculated MRs proved to be similar during alkalinization and during acidification, although there was a tendency to lower excretion of debrisoquine and its 4-hydroxymetabolite into acidic urine. The HPLC analysis correlated well with the GC analysis of debrisoquine and 4-hydroxy-debrisoquine concentrations in urine. The debrisoquine MRs obtained with HPLC and GC also correlated favorably (r = 0.90, p less than 0.001).
Kallio
J
J
Department of Pharmacology, University of Turku, Finland.
D000284:Administration, Oral; D000328:Adult; D000643:Ammonium Chloride / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D003647:Debrisoquin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000652:urine*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000652:urine*; D008297:Male; D010641:Phenotype; D012964:Sodium / Q000494:pharmacology; D017693:Sodium Bicarbonate; D013997:Time Factors
D001639:Bicarbonates; D007546:Isoquinolines; D000643:Ammonium Chloride; C012359:4-hydroxydebrisoquin; D017693:Sodium Bicarbonate; D012964:Sodium; D003647:Debrisoquin