Gram-scale purification of aconitine and identification of lappaconitine in Aconitum karacolicum.

Aconitum karacolicum from northern Kyrgyzstan (Alatau area) contains about 0.8-1% aconitine as well as other aconite derivatives that have already been identified. In this paper, we compare several methods for the further purification of an Aconitum karacolicum extract initially containing 80% of aconitine. Reverse-phase flash chromatography, reverse-phase semi-preparative HPLC, centrifugal partition chromatography (CPC) and recrystallization techniques were evaluated regarding first their efficiency to get the highest purity of aconitine (over 96%) and secondly their applicability in a semi-industrial scale purification process (in our case, 150g of plant extract). Even if the CPC technique shows the highest purification yield (63%), the recrystallization remains the method of choice to purify a large amount of aconitine as i) it can be easily carried out in safe conditions; ii) an aprotic solvent is used, avoiding aconitine degradation. Moreover, this study led us to the identification of lappaconitine in Aconitum karacolicum, a well-known alkaloid never found in this Aconitum species.

Changes in endogenous urea recycling and the handling of renal urea in pregnant and lactating Sardi sheep kept on a constant feeding level.

The kinetics of endogenous urea were compared during the last month of pregnancy, lactation, and a nonpregnant, nonlactating control period in Sardi sheep kept on a constant feed level. Urea entry rate estimated by injections of [14C]urea rose by 36% during pregnancy. Renal urea excretion was reduced by 40% during pregnancy and by 28% during lactation. Consequently, fractional urea recycling was greater during pregnancy and, to some extent, during lactation than during the control period. In a second series of experiments, glomerular filtration rate increased by 48% and urea filtration rate rose by 17% during pregnancy. During lactation, both glomerular filtration rate and urea filtration rate were close to control levels. It appears that the decreased renal urea excretion during pregnancy and lactation was due mainly to increased tubular reabsorption of urea. Rumination time increased by 15% during pregnancy. Rumen ammonia concentration was elevated in both pregnant and lactating ewes above the control period level. The results suggest that Sardi sheep possess a high potential for the conservation of nitrogen during pregnancy and lactation periods.

An in vivo model for pharmacokinetic studies in the kidney.

In order to assess drug renal kinetics in vivo, the two kidneys of seven ewes were surgically placed under the skin. Through the use of renal function tests and a series of biopsies, we found that the kidneys remained normal in their subcutaneous location. Gentamicin renal kinetics were evaluated in conscious animals by a series of biopsies. Histological controls showed only slight lesions due to biopsy; based upon plasma hydrocortisone concentration, there was no indication of chronic stress affecting the renal pharmacokinetics. We suggest that this model has great potential as a method for studying in vivo the kinetics of drug disposition in the renal tissue and assessing the residue level of a drug.

Prednisolone succinate and prednisolone acetate in cattle: pharmacokinetics and action on the adrenal gland.

The pharmacokinetics of prednisolone were studied in a group of 6 cows given prednisolone 21-sodium succinate IV and IM (600 micrograms/kg of body weight expressed as prednisolone alcohol) and prednisolone acetate IM (600 micrograms/kg of body weight expressed as prednisolone alcohol). After IV administration of prednisolone 21-sodium succinate, the half-life of elimination was 3.6 +/- 1.177 hours. After IM administration of prednisolone 21-sodium succinate, absorption was rapid and complete. After IM administration of prednisolone acetate, absorption was very slow with an absorption half-life of 48 hours, but was still complete. Basal plasma hydrocortisone was about 7.5 ng/ml. After IV and IM administration of prednisolone 21-sodium succinate, plasma hydrocortisone returned to normal values within 48 hours. In contrast, after IM administration of prednisolone acetate, a long adrenal suppression lasting from 4 to 6 weeks was observed.

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.