[Clinical study concerning of latamoxef concentration in the obstructed urinary tract].

Urinary LMOX concentration was studied in 18 patients with unilateral ureteral obstruction. The concentration of LMOX in the urine from the mild obstructed kidney was 124 to 2,140 micrograms/ml and 10 micrograms/ml in the severely obstructed ones. The difference was probably due to the intensity and the duration of the obstruction. The patient with 99mTc-DMSA renal uptake of less than 3% also had a urinary LMOX concentration of less than 7 micrograms/ml. The above results seem to show that 7 micrograms/ml in urinary LMOX concentration is a significant figure for treatment of UTI. 99mTc-DMSA renal uptake and renal echogram were used to estimate the excretion rate of antibiotics into the urine.

Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (6): A mechanism for the suppressive action of latamoxef on intrarenal tobramycin level.

The mechanism by which latamoxef (LMOX) reduces intrarenal tobramycin (TOB) levels was studied. When TOB (90 mg/kg/day, s.c.) and LMOX (500 or 2000 mg/kg/day, s.c.) were given simultaneously at separate sites to rats, 20 to 30% reductions in intrarenal TOB concentration were found on the 1st and 3rd days, as compared with the results from using TOB alone. The treatment with the reaction mixture of TOB and LMOX, which was preincubated for 3 hr at 37 degrees C to form the complex of TOB and LMOX, resulted in a greater suppression of TOB level in the kidney than administration of TOB and LMOX concomitantly at separate sites. When LMOX was given to rats 0.5 or 1.5 hr before s.c. injection of TOB, there were significant reductions in intrarenal TOB concentration. However, treatment with LMOX 5 hr before, as well as 1.5 or 5 hr after TOB injection, was ineffective in reducing the accumulation of TOB in the kidney. In the rats given both drugs simultaneously, the urinary excretion pattern of TOB almost overlapped with that of LMOX. Additionally, we detected a complex of TOB and LMOX in the urine of rats given both drugs simultaneously. These results suggest that the suppressive action of LMOX on intrarenal TOB level is due to the interaction of TOB and LMOX.

Epimerization kinetics of moxalactam in frozen urine and plasma samples.

The epimerization of moxalactam (LMOX) in frozen urine and plasma samples was studied during long-term storage. The R/S ratio at equilibrium [(R/S)eq] at -10 degrees C was similar in urine and in rat and human plasma ultrafiltrate but differed from that in water. The (R/S)eq values in human plasma and its ultrafiltrate differed slightly, while they were the same in rat plasma and in its ultrafiltrate. The difference for the human plasma and ultrafiltrate may result from differences in plasma protein binding between R- and S-epimers in the liquid region of the frozen plasma. The change of R/S ratio in frozen human plasma continued below the collapse temperature of LMOX aqueous solution, where the liquid region appeared still to exist as determined by NMR measurement. Consequently, the biological LMOX samples should be preserved at or below -70 degrees C to prevent changes in the R/S ratio.

Disposition of moxalactam and N-methyltetrazolethiol in rats and monkeys.

The disposition of moxalactam (MOX) and N-methyltetrazolethiol (NMTT) in rats and monkeys after intravenous injection was investigated, focusing on the in vivo liberation of NMTT, by using [NMTT-14C]MOX and [14C]NMTT. After [NMTT-14C]MOX injection, MOX levels in plasma quickly became high in both rats and monkeys and then declined, with half-lives at the beta phase of 18.8 and 67.1 min, respectively. The levels of NMTT liberated from MOX were much lower than those of MOX, but the apparent elimination was significantly slow. The levels of MOX and NMTT in rat liver were almost comparable but lower than those in plasma. With [14C]NMTT administration, the level of NMTT in plasma declined, with half-lives at the beta phase of 21.5 min in rats and 54.0 min in monkeys. After [NMTT-14C]MOX injection, most of the radioactivity was excreted in urine as MOX, with 11% of the dose in rats and 8% of the dose in monkeys eliminated as NMTT until 24 h. Total biliary excretion was 26% of the injected radioactivity in rats, and most of it was due to MOX. In one monkey, the total biliary excretion was only 0.2% of the injected radioactivity. With [14C]NMTT administration, most radioactivity was excreted in the urine as unchanged NMTT in both animals. Oral administration in rats showed that part of the biliary-excreted MOX was degraded to NMTT in the intestine and then absorbed. Repeated administration of [NMTT-14C]MOX to rats did not change the levels of MOX and NMTT in plasma or liver nor did it change the excretion profiles. Thus, accumulation of MOX and NMTT did not occur.