Effect of urine pH and ascorbic acid on the rate of conversion of methenamine to formaldehyde.
The kinetics of conversion of methenamine to the active form formaldehyde were studied in pooled urine samples at 37 degrees in the pH range 4.9-6.5. Using a method for the determination of both formaldehyde and unhydrolyzed methenamine, the rate of formaldehyde formation in urine was found to be apparent first order and was pH dependent. Bactericidal concentrations of formaldehyde (> 28 micrograms ml-1) were achieved in 3 h in urine of pH 6.0 containing methenamine at 750 micrograms ml-1. There was no difference in the in vitro rate of conversion of methenamine to formaldehyde between the urine collected from normal subjects and the urine from subjects administered ascorbic acid. The rates of degradation of the mandelate and hippurate salts in buffer systems of various pH values did not differ significantly from those of methenamine base in urine adjusted to the same pH. The half-life of methenamine conversion to formaldehyde increased approximately 20 times from 20 h at pH 5.0 to about 400 h at pH 6.5. The data suggest that unless the urine is maintained below pH 6 only a small fraction of methenamine would be converted daily to formaldehyde and, thus, may explain the need for large doses of this drug in patients.
Strom
J G
JG
Southern School of Pharmacy, Mercer University, Atlanta GA 30341-4155.
Jun
H W
HW
D000892:Anti-Infective Agents, Urinary / Q000652:urine; D001205:Ascorbic Acid / Q000494:pharmacology* / Q000652:urine; D005557:Formaldehyde / Q000652:urine*; D006626:Hippurates / Q000652:urine; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D008333:Mandelic Acids / Q000652:urine; D008709:Methenamine / Q000031:analogs & derivatives / Q000652:urine*
D000892:Anti-Infective Agents, Urinary; D006626:Hippurates; D008333:Mandelic Acids; D005557:Formaldehyde; C023055:methenamine mandelate; D008709:Methenamine; C011481:methenamine hippurate; D001205:Ascorbic Acid