Behaviour of Doxycycline in the Tissues

Abstract

Little is known about the behaviour of antibiotics in the tissues. To investigate this problem, rats were sacrificed in groups of six, 1, 2, 4, 6, 8, 12 and 18 h after an intraperitoneal injection of 10 mg doxycycline/kg body weight. The antibiotic levels were determined in the nine major organs and in the serum by a microbiological method. One hour after injection, the doxycycline concentrations in all the tissues were already higher than the serum concentrations. After 4 h, the concentration exceeded 2.5 μg/ml in the lungs, muscles, testes and heart, and were much greater in the excretory organs: 11.4 ± 4.1 μg/ml in the liver, 10.2 ± 1.6 in the renal medulla and 27.8 ± 7.0 in the renal cortex. Throughout the experiment, the lung and muscle concentrations were about double the serum concentrations, and this occurred with great regularity. Doxycycline is thus capable of penetrating extremely rapidly and intensely into tissues, while still retaining a great degree of freedom of movement between plasma and tissues.

Pharmacokinetics of Ampicillin, Cephalothin and Doxycycline in Various Tissues of the Rat

“…It might have been thought that the same would apply to the tissues, but our observations show that this is not the only factor involved, nor even the principal fac tor. Of the three antibiotics studied here, doxycycline is the one that pene trates best into the tissues, although its plasma protein bound in rats is much greater than that of ampicillin [4].…”

“…The kinetics of doxycycline in excretory organs is complicated and cannot be expressed as straight lines on the semilogarithmic scale [4]. Concentrations in the renal cortex and medulla continued to rise between 2 and 4 h after the injection at a time when the serum levels had already become stabilized.…”

“…In spite of care ful absorption, there is no doubt that urine remained in the homogenate that was analyzed, the antibiotic concentration varying greatly according to the segment of tubules considered. With no other claim than to making a mere approximation, we estimated the amount of doxycycline in the urine retained in the kidney by using, as basis, the creatinine concentration in the homogenates, since the renal clearance of the unbound doxycycline (30%> of the total doxycycline in the rat [4]) is nearly the same as that of substances excreted only by glomerular filtration. On the basis of these measurements, we came to the conclusion that nearly one-tenth of the doxycycline in the cortex homogenates and one-third in the medulla hom ogenates were actually in the residual urine.…”

“…Unfortunately, while we can assess the serum and tissue levels at a given moment on the basis of the availa ble literature [3,5,8,9,11,12,14,19,20,21,24,25], it is exceptional for publications to provide a view of the kinetics of the situation [4,6,13,17,18]. How long does an antibiotic take to start penetrating into the tis sue?…”

Relationships between the Concentrations of Doxycycline in Serum and in Thoracic Duct Lymph after Oral and Intravenous Administration in Man

“…In man, the drug was shown to have an excellent penetration into various organs, the con centrations in several investigated tissues being considerably higher than in serum [3,[8][9][10]14], This seems valid also for poorly vascularized tissue, i.e. the maxillary sinus mucosa during sinusitis [7], In rats, the rate of penetration into tissues was rapid, and the concentrations in serum and several tissues reached their maximum simultaneously [4], If this applies also to man, the concentration of the drug in the tissue fluids could be expected to closely follow that in the serum, and the concentrations in the tissue fluids after a given dose should be of the same magnitude when the distribution phase is completed, irrespective of the mode of administration.…”