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Pharrnacokinetics of nalidixinic acid and oxolinic acid in healthy wornen

The pharmacokinetics of oral nalidixinic acid (NA, 1 gm 4 times a day) and oxolinic acid (OA, 750 mg 2 times a day) administeredfor 7 days were studied in the same 10 healthy women on the first, third, and seventh days of the treatment. The peak concentrations of NA + OH‐NA (hydroxynalidixinic acid) in serum at 2 to 3 hr were 34 µg/ml (total) and 23 µg/ml (unconjugated) on the first day and nearly two times higher on the third and seventh days; 82% to 85% of these amounts were NA. The protein‐free fraction of NA + OH‐NA was 8.8% to 18.3%. The total concentration of NA + OH‐NA in urine was 1,220 to 2,700 µg/ml, the unconjugated concentration, 250 to 350 µg/ml, and the chemotherapeutically active concentration, 55 to 75 µg/ml. In steady state the 24‐hr recovery of the total drug was 79% of the daily dose. The excretion rate in urine was 591 to 853 mg 16 hr. The OA concentration in serum was very low on the first day of the treatment, but increased to 4‐ to 5‐fold on the third and seventh days: 6.2 to 6.4 µg/ml (total) and 3.3 to 3.6 µg/ml (unconjugated). The protein‐free OA represented 19% to 23% of the total amount. The modest initial serum concentrations of OA were conjirmed by the low urine concentrations on thefirst day. In steady state the OA concentration in urine was 570 µg/ml (total) and 35 µg/ml (unconjugated), and the 24‐hr recovery, 49% and 3%, respectively. The microbiologic assay gave somewhat higher concentrations of the active drug than did the chemical assay. When taken with food, the excretion of OA in urine was retarded by 6 hr but the 48‐hr recovery was not decreased.