Developing a single application formulation with a Solanum glaucophyllum extract for milk fever prevention. I: plasma kinetics in dry cows.

Milk fever is a metabolic disease in milk producing cows around calving. Clinical signs are muscular paralysis mainly of the legs with immobility of the affected animal. High milk producing breeds and older animals are most likely affected, and have a high chance of recurrence. An incidence of 5 – 10% has been reported. The disease is caused by an acute drop in blood calcium (Ca) when initiating milk production depletes the blood Ca too fast for repletion from bone mobilization and intestinal uptake. With the understanding of the underlying mechanism, Ca supply management and vitamin-D (VD) supplementation became prime candidates for MF prevention and therapy. Several strategies have been developed for MF prevention e.g. peri-parturient administration of large doses of calcium or an ante-parturient feeding regime known as DCAD. VD as the main calcium regulating agent has also been used. While the efficacy of 1,25D and of the plant Solanum glaucophyllum (SG) in Ca mobilization and MF prevention has been shown, hypocalcaemia has occasionally been observed after cessation of application. Here we present a system which may overcome this limitation by a single bolus containing an immediate and a slow release formulation of a SG extract (SGE).

Tab. 1

	Serum 1,25D1)	Serum Ca	Serum P	Serum Mg	urine Ca/crea	urine P/crea
control	1	1	1	1	1	1
l,25D	2.89	1.07**	1.20*	1.05*	6.98	1.62
irSGE	3.13	1.08*	1.30**	1.01ns	7.21	1.53
srSGE	4.21	1.12**	1.41**	1.04ns	5.40	3.93
	ns	2)	2)	2)
1)Standard deviation not calculated due to pooled serum samples. 2) p-values Mann-Whitney U Test (2-sided) versus control: ** 0.01, *0.05 Post hoc power calculation: 100% for Ca AUC; 100% for P AUC, except for 1.25D vs. control (93%); 15% (srSGE vs. control), 6% (irSGE vs. control) and, 68% 1,25D vs. control for Mg AUC.

A single oral dose was given to 5 non-lactating cows either as synthetic 1,25D, as SGE or as a slow-release form of SGE (srSGE). Ca, P, Mg and 1,25D was measured in serum. Area under the curve (AUC) for 11 days over control for serum Ca, Phosphor and magnesium and for urine Ca and P is given below. AUCs were calculated and normalized to the value of the control group (set to 1).

In the present study shows the retard-release form of the tested srSGE the highest AUC within 11 days after a single application for serum Ca, P and 1,25D.