A selective LC/RIA for dexamethasone and its prodrug dexamethasone-21-isonicotinate in biological fluids.

A combined LC/RIA procedure is described for the selective determination of dexamethasone (DEX) and its prodrug dexamethasone-21-isonicotinate (DIN) in plasma. The low affinity of the employed dexamethasone antiserum for DIN (cross-reactivity less than 0.5%) allowed the direct determination of DEX in plasma extracts. For the determination of DIN, both substances of interest were separated by LC, the DIN containing fraction was collected, hydrolysed and the generated DEX was consequently assayed by radioimmunoassay. The assay detection limits were 0.1 ng ml-1 for DEX and 0.75 ng ml-1 for DIN. For both substances, inter- and intra-day variabilities (RSDs) were 6 and 12%, respectively.

Dexamethasone and prednisolone in the horse: pharmacokinetics and action on the adrenal gland.

Pharmacokinetics of dexamethasone and prednisolone were studied in 6 horses given dexamethasone alcohol (IV or IM) or dexamethasone 21-isonicotinate as a solution IV or IM (50 micrograms/kg of body weight), prednisolone 21-sodium succinate IV or IM (0.6 mg/kg of body weight), or prednisolone acetate IM (0.6 mg/kg of body weight). Plasma concentrations were determined using a high-performance liquid chromatographic method. After dexamethasone alcohol (IV) or dexamethasone 21-isonicotinate (IV), the half-life of elimination was similar (53 minutes) for both formulations. After dexamethasone (alcohol and isonicotinate, IM), concentrations were low or nondetected. After prednisolone 21-sodium succinate (IV), the half-life of elimination (99.5 minutes) was significantly (P less than 0.01) longer than that for dexamethasone. After prednisolone 21-sodium succinate (IM), absorption was rapid and bioavailability was high. After prednisolone acetate (IM), absorption was slow and prednisolone was present in plasma for about 7 days. Due to the nonlinearity of prednisolone kinetics, a bioavailability higher than 100% was obtained. The basal plasma hydrocortisone concentration was approximately 70 ng/ml. After dexamethasone (IV or IM), plasma hydrocortisone values decreased after a 2-hour delay and returned to base line after a 3 to 4 day delay. After prednisolone 21-sodium succinate (IV or IM), plasma hydrocortisone decreased immediately (IV) or rapidly (IM) and returned to base line after a 24-hour delay. After prednisolone acetate (IM), plasma hydrocortisone decreased for up to 21 days.

Dexamethasone concentrations in bovine blood plasma and milk after intravenous injection.

Passage of dexamethasone from plasma to milk in five lactating dairy cows after an intravenous injection was evaluated by a high performance liquid chromatographic technique for measurement of concentrations in blood plasma and milk. The dexamethasone ester was 21-isonicotinate as a solution and was administered at .1 mg/kg bodyweight. The drug was detected in milk postinjection from 15 min to 8 h with a peak concentration of 20.6 ng/ml at the second sample time (30 min). Half-times of dexamethasone in plasma and milk were 4.5 and 3.0 h. The ratio of mean concentration for milk/plasma was .39. It is anticipated that no residues of dexamethasone would be detected in milk if normal dairy practices are followed.

[Penetration of the tympanum by active substances (author's transl)]. / Penetration von Wirkstoffen durch das Trommelfell

In a specially designed animal model the penetration of glucocorticoid and oxytetracycline through the intact tympanic membrane was studied. Dogs were anesthetised for up to 8 h, and the substances were administered to the external auditory meatus. The measured concentration of the applied glucocorticoid in the tympanum showed a level which can be expected to be therapeutically active. When treating the inflamed middle ear, an adjuvant therapy with the combination dexamethasone-21-isonicotinate/oxytetracycline/natamycine/;etracain (Incut) should be taken into consideration. Although oxytetracycline was administered as well, this substance could not be measured in the small samples due to technical reasons. To find out about penetration of o%ytetracycline will have to be the object of another series of experiments.