Intestinal permeability of forskolin by in situ single pass perfusion in rats.

The intestinal permeability of forskolin was investigated using a single pass intestinal perfusion (SPIP) technique in rats. SPIP was performed in different intestinal segments (duodenum, jejunum, ileum, and colon) with three concentrations of forskolin (11.90, 29.75, and 59.90 µg/mL). The investigations of adsorption and stability were performed to ensure that the disappearance of forskolin from the perfusate was due to intestinal absorption. The results of the SPIP study indicated that forskolin could be absorbed in all segments of the intestine. The effective permeability (P (eff)) of forskolin was in the range of drugs with high intestinal permeability. The P (eff) was highest in the duodenum as compared to other intestinal segments. The decreases of P (eff) in the duodenum and ileum at the highest forskolin concentration suggested a saturable transport process. The addition of verapamil, a P-glycoprotein inhibitor, significantly enhanced the permeability of forskolin across the rat jejunum. The absorbed fraction of dissolved forskolin after oral administration in humans was estimated to be 100 % calculated from rat P (eff). In conclusion, dissolved forskolin can be absorbed readily in the intestine. The low aqueous solubility of forskolin might be a crucial factor for its poor oral bioavailability.

A pharmacokinetic study of intramuscular administration of bulleyaconitine A in healthy volunteers.

The pharmacokinetics of bulleyaconitine A (BLA) after a single dose of 0.2 mg intramuscular injection was evaluated in healthy volunteers. Physical exam, vital signs, clinical laboratory tests and electrocardiogram measurements were monitored to assess the safety and tolerance of the drug. The plasma levels of BLA in serial samples, collected over 15 h, were measured by a validated high-performance liquid chromatography (HPLC)-electrospray ionization tandem mass spectrometry (MS-MS) method. It was demonstrated that BLA was absorbed rapidly after intramuscular injection. The pharmacokinetic parameters were as follows: the t(max) value was 0.90+/-0.68 h, the C(max) value was 1.13+/-0.76 ng/ml, the AUC(0-t) was 5.16+/-2.05 ng.h/ml, and t(1/2) was found to be 4.88+/-0.97 h. No subject showed any drug-related clinically significant changes on physical examination, vital signs or laboratory tests. Eight of ten subjects reported a distinct feeling of pain at the site of injection starting approximately at the time of their peak plasma concentration and lasting for 2-6 h. The pain was tolerable, and no subject required additional treatment.