Effect of isoniazid on the pharmacodynamics of cefazolin-induced seizures in rats.
Both isoniazid (INH) and cefazolin (CEZ) can have serious adverse effects on the central nervous system (CNS), causing seizures. In this study, we investigated the effect of INH on the pharmacodynamics of CEZ-induced seizures in rats. Male Wistar rats pretreated with INH (150 mg/kg i.p.) or saline received an intravenous infusion of CEZ at 3.2 g/h/rat until the onset of seizures, then samples of cerebrospinal fluid (CSF), blood (for serum), and brain were obtained immediately. The administration of INH was associated with a reduction in the total dose of CEZ required to produce seizures. The concentrations of CEZ in serum, brain, and CSF in INH-treated rats at the onset of seizures were significantly lower than those in control rats. In rats coadministered with pyridoxine (150 mg/kg s.c.), the concentration of CEZ in CSF at the onset of seizures was significantly higher than that in rats administered INH only. These results suggest that INH potentiates the sensitivity of the CNS to CEZ-induced seizures, and that the increased sensitivity is associated with the inhibition of vitamin B(6) metabolism by INH.
Ishiwata
Yasuyoshi
Y
Department of Hospital Pharmacy, School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Nagata
Masashi
M
Yasuhara
Masato
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism; D002437:Cefazolin / Q000009:adverse effects* / Q000097:blood / Q000134:cerebrospinal fluid; D004357:Drug Synergism; D007538:Isoniazid / Q000009:adverse effects* / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D011736:Pyridoxine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*
D000900:Anti-Bacterial Agents; D002437:Cefazolin; D011736:Pyridoxine; D007538:Isoniazid