Clinical Investigation

Kidney International (1974) 5, 365–371; doi:10.1038/ki.1974.52

Doxycycline pharmacokinetics in the absence of renal function

Andrew Whelton, M Schach von Wittenau, Thomas M Twomey, W Gordon Walker and Joseph R Bianchine

Department of Medicine, Johns Hopkins University School of Medicine and the Johns Hopkins Hospital, Baltimore, Maryland, and the Medical Research Laboratories, Pfizer Inc., Groton, Connecticut

Correspondence: Dr Andrew Whelton, Department of Medicine, The Johns Hopkins Hospital, 601 North Broadway, Baltimore, Maryland 21205, U.S.A.

Received 4 September 1973; Revised 5 October 1973.

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Abstract

Doxycycline pharmacokinetics in the absence of renal function. Doxycycline is a new tetracycline that is now in widespread clinical use. It differs from the other tetracycline drugs in many important respects including small daily dosage schedules, essentially complete upper gastrointestinal absorption and excretory characteristics that are independent of renal function. Our studies demonstrate that in anephric patients and patients with varying degrees of renal function the plasma t½ of biologically active doxycycline is not significantly extended and that in such a clinical situation the usual therapeutic regimen of the drug is necessary. Clearance rate of the compound from the systemic circulation by hemodialysis is only 10ml/min or less. In addition, our investigations identify the importance of the nonhepatic gastrointestinal pathway of elimination of doxycycline from the systemic circulation. Doxycycline therefore appears to be unique among the tetracyclines in that it may be utilized as a drug of choice for the therapy of systemic infections when a tetracycline compound is indicated in the clinical setting of impaired renal function.

Pharmacocinétique de la doxycycline en l'absence de fonction rénale. La doxycycline est une nouvelle tétracycline dont l'usage clinique est maintenant largement répandu. Elle diffère des autres tétracyclines à plusieurs égards importants parmi lesquels la faible posologie quotidienne, l'absorption totale dans la partie haute du tractus digestif et des modalités d'excrétion indépendantes de la fonction rénale. Notre travail démontre que chez les sujets anéphriques et les malades atteints d'insuffisance rénale de sévérité variable la demie vie de la doxycycline biologiquement active n'est pas significativement allongée et que dans ces situations cliniques les modalités thérapeutiques habituelles sont nécessaires. La clearance du composé observée au cours de l'hémodialyse est égale ou inférieure à 10 ml/min. De surcroît nos travaux identifient l'importance de la voie d'élimination hépatique non intestinale de la doxycycline. La doxycycline apparaît donc être unique parmi les tétracyclines en ce sens qu'elle peut être utilisée comme une drogue de choix pour le traitment des infections systémiques quand une tétracycline est indiquée et qu'il existe une altération de la fonction rénale.

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