Pharmacokinetics roxithromycin

Roxithromycin does not interfere with the pharmacokinetics of oral contraceptives (357). 

Kees F, Holstege A, Ittner KP, Zimmermann M, Lock G, Scholmerich J, Grobecker H. Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volnn-teers. Aliment Pharmacol Ther 2000 14(4) 407-12. 

Roxithromycin did not alter the pharmacokinetics of carbamazepine (15) or interact with warfarin, ranitidine, or antacids containing hydroxides of aluminium and magnesium (1). 

In an open, randomized, crossover study in 12 healthy volunteers, roxithromycin did not alter the pharmacokinetics of lovastatin in such a way that dosage adjustment of lovastatin should be necessary during co-administra-tion (17). 

Roxithromycin altered the pharmacokinetics of theophylline, mainly increasing the C ax, prolonging the half-life, and increasing the renal clearance (15). However, while these changes were statistically significant, they were considered clinically irrelevant. There was no effect of roxithromycin on trough concentrations of theophylline. 

Young RA, Gonzalez JP, Sorkin EM. Roxithromycin. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs 1989 37(1) 8-41. 

Bucher M, Mair G, Kees F. Effect of roxithromycin on the pharmacokinetics of lovastatin in volunteers. Eur J Clin Pharmacol 2002 57(11) 787-91. 

Pharmacokinetic Estimates of Roxithromycin after Three Single Doses to Healthy Man... 

The pharmacokinetics of roxithromycin have been assessed in patients with histologically and biologically documented cirrhosis [41]. Although increased to 25.5 hr (vs. 7.9 hr in healthy subjects), (5.8 mg/1), (2.1 hr), and AUCs... 

Markham, A., and Faulds, D. (1994). Roxithromycin An update of its antimicrobial activity, pharmacokinetic properties and therapeutic use. Drugs 48,297-326. 

Birkett, D. J., Robson, R. A., Grgurinovich, N., and Tonkin, A. (1990). Single oral dose pharmacokinetics of erythromycin and roxithromycin and the effects of chronic dosing. Then Drug Monit. 12,65-71. 

Petri, R, and Mazzei, T. (1987). Pharmacokinetics of roxithromycin in renal and hepatic failure and drug interactions. J. Antimicrob. Chemother. 20 (Suppl. B), 107-112. 

Tremblay, D., Verger, C., Saint-Salvi, B., Robinet, D., and Manuel, C. (1988). Pharmacokinetics of roxithromycin in chronic renal insufficiency. Br. J. Clin. Bract. 42 (Suppl. 55), 61-62. 

Suijus, A., Tremblay, D., Saint-Salvi, B., Granier, J., and Lefebvre, M. A. (1986). Pharmacokinetic interaction of a new macrolide, roxithromycin (RU 28965) with theophyllin. Presented at the Third World Conference on Clinical Pharmacology and Therapeutics (Stockholm). Abstr. No. 1203. 

Therapeutic usage of this antibiotic is found in Europe, South America and Japan, where extensive clinical studies have been done. Its pharmacokinetic profile is characterized by high plasma, tissue, and body fluid concentrations and a long half-life of 15 hr [137]. The drug is well tolerated orally at either a dose of 150 mg twice daily or 300 mg once daily, with peak and trough serum concentrations of 7 or 11 pg and 2.5 or 3 pg, respectively [138, 139]. Roxithromycin has proven clinical efficacy in oral and dental infections, upper and lower respiratory tract infections, skin and soft tissue infections, and urogenital infections. 

Nilsen, O.G. Aamo, T. Zahlsen, K. Svarva, P. Macrolide pharmacokinetics and dose scheduling of roxithromycin. Diagn.Microbiol.Infect.Dis., 1992, 15, 71S—76S... 

Aluminium/magnesium hydroxide antacids are reported not to affect the pharmacokinetics of clarithromycin, roxithromycin, or telithro-mycin. 

Boeckh M, Lode H, Hofiken G, E eschlein S, Koeppe P Pharmacokinetics of roxithromycin and influence of H2-blockera and antacids on strointestinal absorption. EurJ Clin Microbiol Infect Dis (1992) 11,465-8. 

Aluminium/magnesium hydroxide antacids may reduce the peak levels of azithromycin. Mylanta can prolong the absorption of erythromycin, but this is unlikely to be clinically important Aluminium/magnesium hydroxide antacids do not appear to significantly alter the pharmacokinetics of clarithromycin, roxithromycin or telithromycin. 

Roxithromycin did not alter the pharmacokinetics or effect of warfarin in one study. However, there are at least 2 published cases of interactions with coumarins, and one report reviewing 16 cases. These are diseussed below. 

Erythromycin is a known inhibitor of the cytochrome P450 isoenzyme CYP3A4. However, this isoenzyme has only a minor role in the metabolism of warfarin , (p.358), specifically the less active R-isomer of warfarin. Consequently, only minor increases in the levels of warfarin have been seen in pharmacokinetic studies, which would generally not be expected to be clinically relevant. However, it is possible that even these small changes might be important in a very few patients, particularly those with a low prothrombin complex aetivity. Other macrolides (azithromycin, clarithromycin, dirithromycin, roxithromycin) have less effect on CYP3A4 than erythromycin, and consequently would be expected to have even less effect on the pharmacokinetics of warfarin or acenocoumarol, which is borne out in the few studies available. Nevertheless, cases of interactions have been reported for nearly all these macrolides. Moreover, one cohort study found that clarithromycin increased the risk of an interaction and erythromycin did not. It is possible that there is some other, as yet unidentified, mechanism involved. Alternatively, it is equally possible that the relatively few cases just represent idiosyncratic effects attributable to other factors, and not to any interaction (see also Coumarins -i- Antibacterials , p.365). 

Paulsen O, Nilssai L-G, Saint-Salvi B, Manuel C, Lunell E. No effect of roxithromycin on pharmacokinetic or i 4iarmacodynamic properties of warfarin and its enantiomers. Pharmacol Taxicol( 9ZZ) 63,215-20. 

Roxithromycin 150 mg twice daily for 8 days did not affect the pharmacokinetics ofa single 200-mg dose of carbamazepine in healthy subjects. " However, there is an isolated report of carbamazepine toxicity (levels increased to 21.7 mg/L) in a patient taking carbamazepine and atorvastatin the day after she started to take roxithromycin 150 mg twice daily. Roxithromycin and atorvastatin were stopped and carbamazepine levels fell to 12.5 mg/L within a day. The increased carbamazepine levels were attributed to the concurrent use of roxithromycin. ... 

Al-Humayyd MS. Pharmacokinetic interactions between erythromycin, clarithromycin, roxithromycin and phenytoin in the rat. Chemotherapy (1997) 43, 77-85. 

A study of roxithromycin 300 mg twice daily with omeprazole 20 mg twice daily or with lansoprazole 30 mg twice daily, for 6 days found that neither PPI significantly affected the pharmacokinetics of roxithromycin. ... 

The pharmacokinetic interactions between clarithromycin and omeprazole, esomeprazole and lansoprazole are established. However, none of the changes reported represents an adverse interaction, but they may help to explain why concurrent use is valuable in the eradication of Helicobacter pylori. Erythromycin is likely to interact similarly, whereas roxithromycin does not. Pantoprazole is not affected by macrolides. 

Billaud E M, Guillemain R, Fertineau N, Kitzis M-D, Dreyfus G, Amrein C, Kreft-Jais C, Husson J-M, Chretien P. Interaction between roxithromycin and cyclosporin in heart transplant patients, Clin Pharmacokinet (1990) 19,499-502. 

Moravek J, MatouSovic K, Prdt V, Sedivy J. Pharmacokinetics of roxithromycin in kidney grafted patients under cyclosporin A or azathioprine immunosupfressicn and in healthy volunteers. IntJ Clin Pharmacol Ther Toxicol (1990) 28,262-7. 

Cases of acnte rhabdomyolysis have been reported between lovas-tatin and azithromycin, clarithromycin, or erythromycin and between simvastatin and clarithromycin or roxithromycin. Macrolide antibacterials have also been potentially implicated in cases of rhabdomyolysis with atorvastatin and pravastatin. Pharmacokinetic stndies sn est that the macrolides increase the levels of the statins metabolised by CYP3A4 (namely atorvastatin, Iovastatin and simvastatin). 

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