Phartmaceutical Evaluation of Hollow-Type Suppositories. Part XIII. Enhanced Rectal Absorption of Insulin in Rabbits from Hollow-Type Suppositories Containing Insulin and Glyceryl-1-monooctanoate.

Abstract

The absorption of two kinds of insulin (from porcine or bovine pancreas) from the rectum of rabbits after the administration of hollow-type suppositories containing insulin and glyceryl-1-monooctanoate (GMO) as an absorption-enhancing agent was investigated. Two types of suppositories were employed: type I containing insulin in an aqueous solution (approx. 25 IU/mg/100 microliters citric buffer solution at pH 3.0) in the cavity of the suppository and GMO mixed with a base material (Witepsol H-15), and type II containing insulin in a crystalline form in the same amount as in type I. Without GMO, the insulin and glucose levels in plasma were unchanged, whereas a marked increase in the plasma levels of insulin and a decrease of glucose concentrations were found following coadministration of insulin and GMO by the type I suppository. Similar enhancement of rectal absorption of insulin was obtained from porcine and bovine sources. In the case of the crystalline insulin, despite the use of the same amount of GMO, porcine insulin was more efficiently absorbed than bovine insulin by the type II suppository. GMO enhances the absorption of insulin in an aqueous solution or a crystalline form, and the dissolution rate of insulin may be an important factor in the rectal absorption of insulin.

Pharmaceutical Evaluation of Hollow-Type Suppotitories. Part XXIII. Pharmacokinetics and Pharmacodynamics of Human Chorionic Gonadotropin (hCG) after Rectal Administration of Hollow-Type Suppositories Containing hCG.

“…The suppositories were administered into the lower part of rectum according to the method described in our previous papers. [6][7][8][9][10] Following the intravenous or rectal administration of hCG, 2 ml of blood samples was collected from the auricular vein using a syringe containing edetate disodium (EDTA-2Na) at predetermined time intervals. These samples were centrifuged at 3000 rpm for 15 min to separate the plasma.…”

“…The advantage of using the hollow-type suppository is that it can eliminate the effect of the heating process on the properties of polypeptide drugs during preparation, and can minimize differences in the release rate of a drug from the dosage vehicle. Previously, we successfully applied these suppositories for the rectal delivery of insulin, 7) recombinant human granulocyte colonystimulating factor (rhG-CSF) 8,9) and elcatonin. 1) However, to our knowledge, no studies on hollow-type suppositories for hCG delivery have been reported to date.…”

Effects of a Calcium-Channel Blocker (CV159) on Hepatic Ischemia/Reperfusion Injury in Rats: Evaluation with Selective NO/pO2 Electrodes and an Electron Paramagnetic Resonance Spin-Trapping Method

“…9) We have been studying the advanced treatment of hepatic I/R injury. 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy) hexyl ester (designated as CV159), which is a 1,4-dihydropyridine derivative, represents a new class of calcium antagonists that function via the selective blockade of Ca 2ϩ /Calmodulin (Ca 2ϩ /CaM).…”

“…The principle of the method used is as described previously. 9,17) NO and oxygen diffuse through the gas-permeable membranes of the working electrodes and are oxidized at the electrodes, thus generating electrical current. The redox currents between the working and counter electrodes were detected using a current-voltage converter circuit, an NO meter (NO-502, Eikoukagaku), and a pO 2 meter (PO 2 -150S, Eikoukagaku).…”

“…8) We previously reported that NO and partial pressure of oxygen (pO 2 ) levels can feasibly be monitored under ischemic conditions in rats with I/R injury of the small bowels by using electrodes selective for NO and O 2 molecules. 9) We have been studying the advanced treatment of hepatic I/R injury. 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy) hexyl ester (designated as CV159), which is a 1,4-dihydropyridine derivative, represents a new class of calcium antagonists that function via the selective blockade of Ca 2ϩ /Calmodulin (Ca 2ϩ /CaM).…”