Doxycycline pharmacokinetics in the absence of renal function

Abstract

The Nijmegen Biomedical Study is a population-based cross-sectional study conducted in the eastern part of the Netherlands. As part of the overall study, we provide reference values of estimated glomerular filtration rate (GFR) for this Caucasian population without expressed risk. Age-stratified, randomly selected inhabitants received a postal questionnaire on lifestyle and medical history. In a large subset of the responders, serum creatinine was measured. The GFR was then measured using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. To limit possible bias, serum creatinine was calibrated against measurements performed in the original MDRD laboratory. The study cohort included 2823 male and 3274 female Caucasian persons aged 18-90 years. A reference population of apparently healthy subjects was selected by excluding persons with known hypertension, diabetes, cardiovascular-or renal diseases. This healthy study cohort included 1660 male subjects and 2072 female subjects, of which 869 of both genders were 65 years or older. The median GFR was 85 ml/min/1.73 m 2 in 30-to 34-year-old men and 83 ml/min/1.73 m 2 in similar aged women. In these healthy persons, GFR declined approximately 0.4 ml/min/year. Our study provides age-and gender-specific reference values of GFR in a population of Caucasian persons without identifiable risk.

Pharmacokinetics and tissue localization of doxycycline polyphosphate and doxycycline hydrochloride in the rat

“…Concentrations in heart and lungs were always higher than in serum which corroborates Fabre's (8) and Cahen's results (19). The penetration of doxycycline into bronchial secretions has also been demonstrated in man (11,12,13) Hartnett (12) has shown that doxycycline remains in sputum for several days after the completion of treatment.…”

Relation Between Lipophilicity and Pharmacological Behavior of Minocycline, Doxycycline, Tetracycline, and Oxytetracycline in Dogs

“…With the exception of absolute renal extraction, there was no correlation between lipophilicity and Doxycycline displayed a marked propensity to accumulate intraluminally in ileal segments containing milk. Such accumulation presumably is the result of the relatively high lipophilicity of doxycycline, permitting its passage across the intestinal mucosa, and its tendency to form complexes with polyvalent cations of metals (41); moreover, the observation is in accord with the finding that substantial amounts of doxycycline may be passively transported from the serum into the intestinal lumen of dogs (37), rats (38), and humans (41). Although the data of Table 1 suggest that doxycycline is somewhat less readily chelated by calcium than is oxytetracycline or tetracycline, other work indicates that at approximately neutral pH, the tetracyclines are almost completely chelated by all polyvalent metallic cations studied (1,2,4).…”

“…Many of these objectives have been met in minocycline and doxycycline (6,9,10,25,26,34,41). Of additional interest is the fact that neither of these tetracyclines appears to require a major adjustment in dose in the presence of renal failure (6, 41), suggesting that they are extensively eliminated by nonrenal routes.…”

“…Of additional interest is the fact that neither of these tetracyclines appears to require a major adjustment in dose in the presence of renal failure (6,41), suggesting that they are extensively eliminated by nonrenal routes. Doxycycline has been demonstrated to be excreted extensively via the intestine (41). The data relative to minocycline, however, are inconclusive, and biliary excretion (29), intestinal excretion (6), and metabolic degradation (25) have all been considered as possible modes of nonrenal elimination of this agent.…”

The effects of chronic renal insufficiency on the pharmacokinetics of doxycycline in man.

“…Doxycycline has several important advantages over other tetracycline analogues: absorption is almost complete (90-95%), tissue penetration, even if structurally modified by inflammation, is facile, elimination is slower, necessitating only one daily dose of 100 mg, and urine concentrations are higher yielding good results in the therapy of urinary tract infections (Schach von Wittenau & Delahunt, 1966;Fabre et al, 1967). Although 30% to 50% of administered doxycycline is normally excreted unchanged in the urine, it does not accumulate in cases of renal insufficiency and therefore has been extensively used in patients suffering from various degrees of renal impairment or even in anuric patients (Merier et al, 1969;Ritzerfeld et al, 1970;Whelton et al, 1974;Simon et al, 1975).…”