Pharmacokinetics and bioavailability of doxycycline in humans.

The bioavailability of a new tablet of 6-deoxy-5-hydroxytetracycline (doxycycline, Doxycline Plantier) was estimated relatively to an oral solution and a commercially available capsule. Each form was administered to 12 healthy volunteers according to a replicated latin square. Statistical analysis of non-compartmental pharmacokinetic parameters - maximum concentrations, corresponding time, area under the plasma concentrations curve and unchanged amounts recovered in the urine - failed to show any difference between the tested pharmaceutical forms, although the new tablet allows to reach higher concentrations.

Alpha 1- and alpha 2-adrenoceptor selectivity of moxisylyte (thymoxamine) and its metabolites in the pithed rat.

The selectivity of moxisylyte and its two metabolites deacetylmoxisylyte and demethyldeacetylmoxisylyte, for alpha 1- and alpha 2-adrenoceptors has been investigated in the pithed rat. Alpha 2-adrenoceptor blockade was measured by antagonism of the inhibitory effect of clonidine on the tachycardia produced by electrical stimulation of the cardiac accelerator nerves and of the pressor response to B-HT 933. alpha 1-Adrenoceptor blockade was measured by inhibition of the pressor response to (-)phenylephrine and to stimulation of the sympathetic outflow from the spinal cord. The three drugs (5 X 10(-6) to 2 X 10(-5) mol/kg i.v.) did not affect the inhibitory effect of clonidine and were equipotent as antagonists of the pressor response to B-HT 933, but only at the higher dose (10(-5) mol/kg). Moxisylyte and its metabolites (2.5 X 10(-6) to 10(-5) mol/kg i.v.) reduced the pressor response to (-)phenylephrine and to stimulation of the sympathetic outflow of the spinal cord in a dose-dependent manner. They were much more effective against (-)phenylephrine than B-HT 933. These results indicate that the three drugs are preferential alpha 1-adrenoceptor antagonists in vivo.

Pharmacokinetics of arginine and aspartic acid administered simultaneously in the rat--III: Changes in the levels of amino acids in the plasma, liver and brain after simultaneous administration of arginine and aspartic acid.

Changes in the levels of amino acids in the plasma, liver and brain were studied in rats after simultaneous administration of 0.1 mmol/rat of arginine and aspartic acid. The levels of most of the assayed amino acids underwent various changes some of which only occurred in one of the organs studied, for example, GABA in the brain and proline in the liver. It is difficult to advance any explanation. Meanwhile some of changes can be explained on the grounds of well-known metabolic changes. The large increase of ornithine in the liver may be due to the action of arginase in the first stage in the urea cycle. This amino acid is the precursor of glutamic acid and proline which may explain the high levels of these two amino acids observed especially in the liver. The increase of GABA in the brain may be due to the simultaneous administration of arginine and aspartic acid which could induce the formation of ornithine and alpha-ketoglutaric acid respectively, two metabolites known to increase cerebral GABA. The increases in Ser, Gly, and Ala observed in practically all the tissues studied may be due to the formation of oxaloacetate from aspartic acid.

Pharmacokinetic study of doxycycline polyphosphate+ after simultaneous ingestion of milk.

Pharmacokinetic parameters of doxycycline polyphosphate were studied in healthy volunteers after oral administration of a single 200 mg dose of this antibiotic with a breakfast containing or not 200 ml of whole milk. Ingestion of milk had only mild effect upon absorption parameters of doxycycline; only a moderate increase of the lag-time was significant. Elimination parameters of doxycycline were impaired by milk; a decrease of the terminal half-life from 28 h to 15 h, and apparent decrease of the enterohepatic circulation and an increase in total body clearance from 40 to 62 ml/min. were observed.

Pharmacokinetics of doxycycline polyphosphate after oral multiple dosing in humans.

Nine healthy volunteers received oral multiple doses of doxycycline polyphosphate for 6 days. Three different dosage schedules were given and the time concentration data obtained was used to determine the best protocol for producing effective serum antibiotic levels during a complete period of treatment with the aid of a mathematical simulation programme. This protocol consisted of the administration of a 200 mg loading dose on the first day, followed by a 100 mg maintenance dose every twelve hours. Using this dosage schedule a steady state was obtained on the first day of treatment, 3 mg/l was the maximum serum level reached, and the lowest serum concentration was more than 1 mg/l which was assumed to be a therapeutically effective serum concentration.

Pharmacokinetic study of doxycycline polyphosphate (PPD), hydrochloride (CHD) and base (DB).

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.