Pharmacokinetics of Nalidixic Acid in Old and Young Volunteers

Abstract

Plasma levels of active naphthyridine were measured in healthy old (mean age 77.3 years) and young (mean age 25.4 years) subjects following oral administration of 1 Gm nalidixic acid. The plasma levels of active naphthyridine, i.e., nalidixic acid and its metabolite 7-hydroxynalidixic acid, were generally higher in the old group, particularly in the elimination phase. Significant variations in the pharmacokinetic parameters were obtained between the two groups of volunteers. The plasma half-life of active naphthyridine averaged 11.5 hours in old subjects and 2.7 hours in the younger group. Diminished renal function in the geriatric group may explain the slower elimination of the drug in the old subjects. The mean values of the other parameters calculated were: apparent volume of distribution, 0.55 (old) and 0.47 (young) liter/kg body weight; area under the curve, 327.7 (old) and 156.3 (young) micrograms/ml x hr; total body clearance 2.9 (old) and 8.3 (young) liters/hr; absorption rate constant, 0.29 (old) and 0.52 (young) hr. -1

Pharmacokinetics, bioavailability, plasma protein binding and disposition of nalidixic acid in Rainbow Trout (Oncorhynchus mykiss)

“…T h e total body clearance (31.5 ml/kg/h), however, was much smaller than the intercompartmental clearance rate (Cl,) (1946.1 f 21 3.6 ml/kg/h) suggesting that the former controls elimination of the drug. Interestingly, total body clearance of NA in mammals was shown to be 93-262 times faster than the values reported here for trout (Barbeau and Belanger 1982).…”

“…Such data suggests that NA was widely distributed into all fluid spaces. This volume of distribution was much larger than that reported for dog (264 ml/kg) (Nakamura et a2.1985) and man (470-550 ml/kg) (Barbeau and Belanger 1982) but significantly smaller than the V,, of oxolinic acid (1 81 7 ml/kg) reported for trout (Kleinow et al 1992b). Discrepancies between trout and mammalian volume of distribution values for NA may in part be related to the large differences which exist in plasma protein binding (trout 26%, man 93%; Portmann et al 1966).…”

“…This compares with NA bioavailabilities in man and beagle of 96 (Barbeau and Belanger 1982) and 63.8% (Nakamura et al 1985), respectively. While the results in the present study indicate that NA upon oral administration is largely bioavailable, the percentage > 100% suggests that either non-linear pharmacokinetics have been evoked or drug clearance varied significantly between i.v.…”

“…The relative quantitative relationship of t I l z , for these two drugs although not identical was similar to that observed in mammalian species. In both cases longer t l l Z p s were observed for oxolinic acid as compared with NA (Mannisto 1976 on the basis of NA tl,2gs, beagle (1.15-1.51 h) (Nakamura et al 1985) and man (2.5-1 1.5 h) (Mannisto 1976, Barbeau andBelanger 1982) consistently demonstrated shorter half-lives than the 23-0-h value observed for trout. The reasons for these findings were not clearly apparent from the current study or the literature.…”

Selective gut decontamination with nalidixic acid or trimethoprim-sulfamethoxazole for infection prophylaxis in neutropenic cancer patients: relationship of efficacy to antimicrobial spectrum and timing of administration

“…Furthermore, TMP-SMX was more protective at neutrophil counts of <0.1 x 109/liter and appeared to delay the onset of infection longer than did nalidixic acid. We feel that the observed differences in microbiologically documented infections and infection-related mortality reflect the wider antibacterial spectrum (1, 7), wider volume of distribution, and superior tissue penetration of TMP-SMX (2,11) than of nalidixic acid.…”