Comparative pharmacokinetic profiles of Cinoxacin and pipemidic acid in humans

Abstract

Serum and urinary levels of Cinoxacin and pipemidic acid were determined at 7-day intervals in the same 10 healthy volunteers after a single oral dose of respectively 500 and 400 mg of the drugs. Comparison of results shows that Cinoxacin was absorbed faster (absorption half-life, ta 1/2cin = 0.25 h) than pipemidic acid (ta 1/2pip = 0.37 h) and distributed in a smaller apparent volume (AVDcin = 23.5 1/1.73 m2; AVDpip = 60.1 1/1.73 m2). Biological half-lives were identical (tb 1/2cin = 2.10 h; tb 1/2pip = 2.15 h). On the other hand, serum levels for Cinoxacin at 1, 2 and 4 hours (8.1 +/- 1.5 micrograms/ml, 10.6 +/- 1.5 micrograms/ml, 5.6 +/- 1.3 micrograms/ml respectively) were higher than those for pipemidic acid (3.3 +/- 0.3 micrograms/ml, 3.4 +/- 0.5 micrograms/ml, 2.1 +/- 0.5 micrograms/ml respectively). Urinary excretion of the two derivatives during the 12 hours following their administration was similar (Ucin0-12h = 86%; Upip0-12h = 83%). Mean urinary concentrations were particularly high, still attaining respectively 90 +/- 29 micrograms/ml and 131 +/- 38 micrograms/ml in samples collected between the 9th and the 12th hours; these levels were well above the M.I.C. for the Gram-negative organisms included within the spectrum of activity of these two quinolones. In addition, predictive calculations of serum levels reached after multiple dosing indicate that at an administration rate of 500 mg every 6 or preferably every 4 hours, Cinoxacin concentrations should be sufficiently high to be of interest in the treatment of systemic infections by sensitive organisms.

Pharmacokinetics of Cinoxacin in Elderly Patients following Repeated Oral Administration

“…This shifting in the time of the peak of the serum levels seems not to affect signifi cantly the height of the peak level which, in our case, is 14.00 ± 3.29 ¡ig/ml after the first administration of cinoxacin, a value comparable to that obtained by other in vestigators [1,2,6], In these elderly patients both the sys temic clearance (1st day 6.55 ± 1.16 liter/h; 7th day 6.38 ± 1.16 liter/h) and the renal clearance (7th day 3.97 ±0.67 li ter/h) are slower than those found in younger people [2,11]. However, the sys temic clearance is found unchanged after multiple administration.…”

“…Moreover, the elimination rate con stants (Kc) calculated at the first and at the last dose (table I) are identical and equiva lent to those found for young people [2,11]. These are useful findings indicating that cinoxacin treatment in elderly pa tients does not require any adjustment of the dose regimen at least in patients with apparently normal creatinine clearance indicating a still acceptable kidney func tion as in the patients under investigation.…”

“…Considering the pharmacokinetic find ings obtained with cinoxacin in aged pa tients and trying to correlate them with the above-mentioned modifications in the pharmacokinetic behaviour of elderly people, a slightly decreased absorption rate may be observed in our patients as the Tmax is reported to be on an average of 2-3 h with a higher absorption rate [1,2,6]. This shifting in the time of the peak of the serum levels seems not to affect signifi cantly the height of the peak level which, in our case, is 14.00 ± 3.29 ¡ig/ml after the first administration of cinoxacin, a value comparable to that obtained by other in vestigators [1,2,6], In these elderly patients both the sys temic clearance (1st day 6.55 ± 1.16 liter/h; 7th day 6.38 ± 1.16 liter/h) and the renal clearance (7th day 3.97 ±0.67 li ter/h) are slower than those found in younger people [2,11].…”

Ciprofloxacin biliary disposition in cholecystectomised patients with special references to HPLC and bioassay data

“…The mathematical calculation of the constants and pharmacokinetic parameters was performed referring to previously published papers (5)(6)(7)18 …”

Single- and multiple-dose pharmacokinetics of pipemidic acid in normal human volunteers

“…The studies performed on patients with impaired renal function (8, 12, 12a, 18) are more comprehensive than those performed on healthy subjects (2,3,13,16). The bioavailability of PPA has been determined only on the basis of its excretion in urine and except for certain urinary data (3), there are no studies of PPA kinetics at steady state.…”