Pefloxacin Theophylline

The quinolones have been found to cause erosion of cartilage in the joints of immature animals [56]. This observation, which has been seen in several studies, has resulted in the contraindication of quinolones for the treatment of children. A study analyzing the risk-benefit situation for the use of pefloxacin in children (clinically, several adverse athralgic effects have been attributed to this agent) has appeared [57]. The underlying mechanism responsible for these effects has yet to be established, and the development of an agent which is safe for paediatric use would be a major advance in quinolone therapy. Some of the quinolones, such as enoxacin, have been shown to interfere with theophylline metabolism [58], and side-effects associated with this agent may be related to this property. 

The interaction between the quinolone antibacterials and CYP1A2 has been studied in some depth for enoxacin and pefloxacin. Both compounds have been shown to inhibit CYPlA2-mediated metabolism of caffeine in vitro (49). This in vitro inhibition translated into a twofold decrease in caffeine clearance by pefloxacin and a sixfold decrease in clearance by enoxacin (50). Because pefloxacin undergoes N-demethylation to norfloxacin (51) and norfloxacin is much more potent as an inhibitor than pefloxacin (50), the observed in vivo interaction seen for pefloxacin may, in part, be due to norfloxacin. Many other quinolone antibacterial agents have been investigated for their interaction with theophylline, and ciprofloxacin has also been shown to have notable inhibitory effects (52). 

Levasseur LM, Delon A, Greco WR, Faury P, Bouquet S, Couet W. Development of a new quantitative approach for the isobolographic assessment of the con-vulsant interaction between pefloxacin and theophylline in rats. Pharm Res 1998 15 1069-76. 

Brochot C, Marchand S, Couet W, Gelman A, Bois FY. Extension of the isobolographic approach to interactions studies between more than two drugs Illustration with the convulsant interaction between pefloxacin, norfloxacin, and theophylline in rats. J Pharm Sci 2004 93 553-62. 

An isolated report describes convulsions in a patient, which were attributed to the use of theophylline with pefloxacin."... 

Conri C, Lartigue MC, Abs L, Mestre MC, Vincent MP, Haramburu F, Constans J. Convulsions chez une malade traitee par pefloxacine et theophylline. Therapie (1990) 45, 358. 

Noninterfering amikacin, aztreonam, carbamazepine, cephalosporins, ciprofloxacin, clavulanic acid, difloxacin, digitoxin, digoxin, fleroxacin, fosfomycin, furosemide, gentamicin, imipenem, lidocaine, netilmicin, norfloxacin, ofloxacin, pefloxacin, penicillins, phenobarbital, phenytoin, primidone, procainamide, quinidine, rifampin, salicylic acid, teicoplanin, theophylline, tobramycin, valproic acid, vancomycin... 

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