Two doxycycline derivatives Doxycycline polyphosphate and Doxycycline hydrochloride were administered to rats at a dose of 20 mg/kg body weight. Doxycycline tissue levels were determined using a microbiological assay. Only an insignificant fraction of the antibiotics was found to cross the blood brain barrier. Doxycycline was highly concentrated in excretory organs: liver, kidneys and caecum. The high intestinal drug level observed is probably related to the entero-hepatic cycle of this antibiotic. There was a good correlation between serum and heart doxycycline concentration; heart level was about twice that of serum. In lung, antibiotic level was always higher than in serum.

Serum kinetics of Doxycycline polyphosphate (DPP) have been studied in dogs after oral administration of 10 mg.kg-1 by measurement of total serum concentration (Ct) of tetracycline derivatives by a chemical assay and active concentration (Ca) by a microbiological method. Kinetics have been studied using a one compartment open model with absorption by oral route. DPP is rapidly absorbed, the peak serum level is reached three hours after absorption and slowly eliminated (elimination half-life = 12 hours). The main differences observed between Ct and Ca kinetics are in the values of the areas under the curves (AUC) and the peak serum level. The values obtained for these parameters for Ca kinetics were found to be 50% of those obtained for Ct, the volumes of distribution being in inverse proportion. These results are in a good agreement with the correlation and linear regression observed between Ca and Ct showing that 55% of total serum Doxycycline possesses immediate antibacterial activity. It is postulated that this difference between Ct and Ca kinetics is essentially a reflection of the ratios of bound and free drug. Similar results were obtained with the finished pharmaceutical form except for a 15% increase of AUC indicating improvement of the bioavailability of the drug.

Obtaining and sustaining an erection are common problems for the male spinal cord injury patient. Intracavernous injection of vasoactive substances offers a new treatment option but it must be approached with caution in this population. In this work, the use of an alpha-adrenergic blocking agent, moxisylyte, after intracavernous administration for complete paraplegic patients with erectile impotence is described. During this study, the pharmacokinetic profile of moxisylyte has been defined. Unchanged moxisylyte is not found in plasma, this drug is immediately metabolized after administration. Three metabolites were found in plasma: desacetylmoxisylyte (DAM), conjugated DAM, and conjugates of desmethylated DAM (MDAM). Maximum plasma levels of 72.3 ng ml-1, 301.4 ng ml-1, and 88.8 ng ml-1 are obtained 0.22 h, 0.9 h, and 2.08 h after drug administration for these three metabolites, respectively. The elimination half-lives are 0.89 h, 2.16 h, and 5.32 h and the MRT, 1.38 h, 3.23 h, and 8.45 h, respectively. No side-effects were noted, only one patient presented sleepiness. Successful erections (10 to 25 min) were obtained in all patients and no priapism was noted.

Six healthy volunteers received the same oral dose of doxycycline, base (200 mg). Each received two of the three preparations at two-week intervals. Experimental results were interpreted on the basis of one or two-compartment models. The three preparations gave the elimination constants of the same order of magnitude (0.045 h-1 to 0.051 h-1). The plasma half-life t 1/2 beta was 14.143 h for DP, 15.400 h for DHC and 13.588 h for DB. Vd is higher for DB (91.955 L) than for DPP (73.401 L) and DHC (64.827 L). Total plasma clearance is 52.767 ml/min for DPP, 48.728 ml/min for DHC and 60.174 ml/min for DB. Urinary elimination 72 hours after administration is 29.24% for DPP, 35.60% and 28.15% for DB. Fluorimetric analysis of some of the samples confirmed the values obtained, with the exception of a few parameters such as Vd and clearance, which were lower. This may result from the fact that this method of determination is more broadly responsive, and is not limited to the evaluation of the active fraction. Relative bioavailability of the capsule form of DPP is 111.15% of that of DHC.

No abstract