In vitro release of tetracyclines in presence of H2-receptor antagonists.

There are a number of drug interactions reported for tetracyclines with many other drugs. In present study in vitro release of five different tetracyclines i.e., tetracycline, demeclocycline, oxytetracycline, methacycline and doxycycline in presence of cimetidine and ranitidine has been studied by USP XX dissolution method. The release of almost all tetracyclines was depressed in presence of cimetidine and ranitidine while in some cases the value were greatly increased due to the formation of charge transfer complexes of the antibiotic with H2-receptor antagonists, which gave absorbance at same wavelengths but with much higher molar absorptivity. An attempt was made to elucidate the mechanism of this effect.

Systemic release of corticosteroids following intra-dental use.

Concern has been expressed in the past that the use of corticosteroids within root canal medicaments or pulp capping agents may lead to deleterious systemic effects. Calculations of the highest possible amounts that could be used, plus an analysis of the release and diffusion characteristics, and comparisons with known endogenous levels of corticosteroids, reveal that the intradental use of Ledermix paste and Ledermix cement is unlikely to result in any systemic side-effects.

Effects of combining Ledermix and calcium hydroxide pastes on the diffusion of corticosteroid and tetracycline through human tooth roots in vitro.

A 50:50 mixture of a corticosteroid/antibiotic paste and calcium hydroxide has been used clinically as a root canal dressing agent. This study investigated the effect on the release and diffusion of the corticosteroid and antibiotic components of Ledermix paste when it was mixed with a calcium hydroxide-methyl cellulose paste. The release rates of the trace molecules were lower when the mixture was used compared with release from Ledermix alone. The results indicated that this combination of materials, when used a long-term intracanal dressing, was likely to be more effective than Ledermix alone.

Disposition kinetics and distribution of demeclocycline in various biological fluids in female goats.

A pharmacokinetic study of demeclocycline was carried out following intravenous administration at 5 mg/kg body weight in lactating goats. Demeclocycline appeared within 5 min in plasma, interstitial fluid (isf) and urine, while it appeared at 1 h in milk. Peak concentrations of 21.70 +/- 4.06, 2.67 +/- 0.23, 5.65 +/- 0.45 and 82.23 +/- 10.06 micrograms/ml were attained at 5 min and at 6, 8 and 8 h in plasma, isf, milk and urine respectively. A potentially therapeutic concentration of greater than or equal to 0.5 micrograms/ml was maintained from 5 min-36 h, 30 min-30 h, 1-36 h and 5 min-48 h in plasma, isf, milk and urine respectively. The drug was detectable in all the above biological fluids for at least 48 h. A low distribution half life (t1/2 alpha) of 0.44 +/- 0.04 h and a high elimination half life (t1/2 beta) of 19.24 +/- 1.22 h denote rapid distribution but very slow elimination of the drug in goats. A high tissue plasma concentration ratio [K12:(K21-beta)] of 5.12 +/- 0.97 during the elimination phase and a Vdarea of 1.59 +/- 0.18 L/kg indicate uniform distribution of demeclocycline in the tissues and body fluids of goats. The dosage regimen for maintaining minimum plasma concentration (Cp infinity min = MIC) of 0.5, 1.0 and 1.5 micrograms/ml at selected dosage intervals of 12 and 24 h was also calculated.