Doxycycline pharmacokinetics

In a pharmacokinetic study [49], this and related aspects of doxycycline were studied in man. Although the degree of serum protein binding as estimated by these workers was lower than in the report [41] discussed above, the differences seem inadequate to call in question the validity of their conclusions in addition, serum levels and protein binding data are not, of themselves, reliable indicators of therapeutic potential. 

Fabre, J., Blanchard, P. and Rudhardt, M., Pharmacokinetics of ampicillin, cephal-othin and doxycycline in various tissues of the rat. Chemotherapy, 23, 129, 1977. Maza, A. et al., Influence of partial hepatectomy on theophylline pharmacokinetics in rats, J. Pharm. Sci., 85, 1133, 1996. 

Pharmacokinetics. Most tetracyclines are only partially absorbed from the alimentary tract, enough remaining in the intestine to alter the flora and cause diarrhoea. They are distributed throughout the body and cross the placenta. Tetracyclines in general are excreted mainly unchanged in the urine and should be avoided when renal function is severely impaired. Exceptionally, doxycycline and minocycline are eliminated by nonrenal routes and are preferred for patients with impaired renal function. 

A 17-year-old girl with a femoral osteosarcoma received her 11th cycle of methotrexate and simultaneously oral doxycycline 100 mg bd for a palpebral abscess. As in previous cycles, pharmacokinetic monitoring of methotrexate was performed. On this occasion the half-life of methotrexate was more than doubled. She developed hematological and gastroenterological toxicity. 

Gastearena, I. Dios-Vieitez, M.C. Segura, E. Goni, M.M. Renedo, M.J. Fos, D. Determination of doxycycline in small serum samples by liquid chromatography. Application to pharmacokinetical studies on small laboratory animals. Chromatographia, 1993, 35, 524-526... 

B. Pharmacokinetics Oral absorption is variable, especially for the older drugs, and may be impaired by foods and multivalent cations (calcium, iron, aluminum). Tetracyclines have a wide tissue distribution and cross the placental barrier. All of the tetracyclines undergo entero-hepatic cycling. Doxycycline is excreted mainly in feces the other drugs are eliminated primarily in the urine. The half-lives of doxycycline and minocycline are longer than those of other tetracyclines. 

Craig N K Jaffe JM, Colaizzi JL and Foust RI, Effect of altered urinary pH on tetracycline and doxycycline excretion in humans, J. Pharmacokinet. Biopharm., 1, 267-282 (1973). 

Anadon A, Martinez-Larranaga MR, Diaz MJ, Bringas P, Fernandez MC, Fernandez-Cruz ML, Iturbe J, Martinez MA, Pharmacokinetics of doxycycline in broiler chickens. Avian Pathol. 1994 23 79-90. 

A study into the effects of alcohol on doxycycline and tetracycline pharmacokinetics found that the half-life of doxycycline was 10.5 hours in 6 alcoholics (with normal liver function) compared with 14.7 hours in 6 healthy subjects. The serum doxycycline levels of 3 of the alcoholic patients fell below the generally accepted minimum inhibitory concentration at 24 hours. The half-life of tetracycline was the same in both groups. All of the subjects were given doxycycline 100 mg daily after a200-mg loading dose, and tetracycline 500 mg twice daily after an initial 750-mg loading dose. ... 

Another study in healthy subjects found that cheap red wine, but not whisky (both 1 g/kg) delayed the absorption of doxycycline, probably because of the presence of acetic acid, which slows gastric emptying. However, the total absorption was not affected. The authors concluded that acute intake of alcoholic beverages has no clinically relevant effects on the pharmacokinetics of doxycycline. ... 

An in vitro study found that doxycycline potentiated the antimalarial activity of atovaquone, but there appears to be no information on the effect of doxycycline on the absorption of atovaquone. A study looking at the population pharmacokinetics of atovaquone in 24 Thai patients found that neither the oral clearance nor the volume of distribution of atovaquone were significantly affected by the concurrent use of tetracycline. ... 

Doxycycline does not appear to alter the pharmacokinetics of quinine. Tetracycline increases quinine levels and has been found to improve efficacy. 

In a study in 13 patients with acute falciparum malaria, the addition of intravenous doxycycline to treatment with intravenous quinine did not affect quinine pharmacokinetics, when compared with 13 patients taking... 

Nguyen VX, Nix DE, Gillikin S, Schentag JJ. Effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline. Antimicrob Agents Chemother (1989) 33, 434-6. 

Venho VMK, Salonen RO, Mattila Ml. Modification of die pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal. EurJ Clin Pharmacol (1978) 14, 277-80. 

Garraffo R, Dellamonica P, Fournier JP, Lapalus P, Bernard E. The effect of rifampicin on the pharmacokinetics of doxycycline. Infection (1988) 16, 297-8. 

Isolated cases suggest that doxycycline and tetracycline can increase the effects of coumarins. Similarly, some small studies (none controlled) suggest that chlortetracycline (alone or with oxytetracycline), doxycycline, or the tetracyclines as a class may increase the risks of over-anticoagulation, but there appear to be no studies of the effect of tetracyclines on the pharmacokinetics of coumarins. However, the related antibacterial, tigecycline, increased the AUC of warfarin, and has been shown to increase the prothrombin time when given alone. 

Iven H, BraschH. Influence of the antibiotics piperacillin, doxycycline, and tobramycin on the pharmacokinetics of methotrexate in rabbits. Cancer ChemoAer Phamacol (i9Z6) 17, 218-22. 

Dogterom P, van den Heuvel MW, Thomsen T. Absence of phannacokinetic interactions of the combined contraceptive vaginal ring NuvaRing with oi amoxicillin or doxycycline in two randomised trials. CUn Pharmacokinet(2005) 44,429-38. 

Pharmacokinetic data show that the progestogen component (levonorg-estrel, norethisterone) of combined oral contraceptives is not affected by ampicillin, clarithromycin, doxycycline, metronidazole, moxi-floxacin, or tetracycline. There is no reason to expect that the contraceptive efficacy of the various progestogen-only methods (tablets, implants, injections, lUDs) would be affected by antibacterials that alter gut flora and do not induce liver enzymes. 

Jonkman JHG, van der Boon WJV, Schoenmaker R, Holtkamp A, Hempenius J. No influence of doxycycline on theophylline pharmacokinetics. TherDrugMonit 9%5) 7, 92-4. 

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