Absorption of cyclosporin from conventional and new microemulsion oral formulations in liver transplant recipients with external biliary diversion.

Abstract

1 Less than 5% of a dose of the conventional oral formulation of cyclosporin, Sandimmun®, is absorbed in liver transplant recipients with external biliary drainage, necessitating intravenous administration of the drug and exposing the patient to increased risk of severe side-effects. 2 We compared the pharmacokinetics of the conventional oral formulation of cyclosporin with that of the new microemulsion formulation, Neoral®, in eight liver transplant recipients with external biliary diversion. Patients were maintained on a continuous infusion of cyclosporin until steady-state conditions had been achieved. They were then given a test dose (10 mg kg-') of either the conventional or microemulsion formulation (randomised order) followed by the same dose of the other formulation. Parent cyclosporin concentrations were measured in whole blood samples collected at timed intervals over the 24 h after the oral doses and pharmacokinetic parameters calculated. 3 The bioavailability of cyclosporin from the microemulsion formulation was, on average, 6.5-fold (95% C.I. 1.9 to 11.1-fold) greater than that of the conventional formulation, indicating the improved absorption characteristics of the new oral microemulsion formulation during external bile drainage. 4 A significant negative correlation was found between the external bile drainage volume and bioavailability of cyclosporin from the microemulsion formulation (r = -0.8; P = 0.016), suggesting that variability in cyclosporin absorption from the microemulsion formulation may still be at least partly attributable to biledependence. Paradoxically, no relationship was found between bile volume and the very low cyclosporin bioavailability from the conventional formulation, perhaps because the volume of bile reaching the gut was below a threshold required for any consistent degree of cyclosporin absorption from this formulation to occur.5 In conclusion, the use of the new oral microemulsion formulation of cyclosporin should help to minimise the problems of cyclosporin malabsorption in most patients with external biliary drainage following liver transplantation. This will reduce requirements for the initial use of the i.v. formulation with its attendant side-effects and so may also reduce hospital stay.

A fehérje–ciklodextrin kölcsönhatás terápiás és diagnosztikai jelentősége

“…9 A detergens és koszolvens tipusú adalékok ismert háránya, hogy parenterális úton adva az excipiensek számos kellemetlen mellékhatát okoznak. 10 Japán és finn kutatók ismerték fel elsõként, hogy a ciklosporin vízoldékonysága alfaciklodextrinek, különösen a 2-hidroxipropil-alfaciklodextrin jelenlétében oly mértékben nõ, hogy az már a terápiás használhatóságot is biztosítja.…”

“…egy ciklodextrin, lehetõvé teszi a szûkített póruson áthaladó molekulák azonosítását. (9. ábra) 9. ábra Az alfa hemolizin és benne ülõ ciklodextrin sematikus szerkezete A: szembõl nézve, B: felülrõl nézve 21 .…”

“…These formulations, however, have several side-effects. 9 Japanese and Finnish researchers recognized first that the solubility of cyclosporine can be improved to the therapeutically desired level by alpha-CD, especially with hydroxypropyl alpha-CD (HPACD). The aggregation of TT232, a stomatostatin analog heptapeptide, can be effectively hindered by methyl beta-CD.…”

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“…Microemulsification times were measured visually observing the mixture and percent transmittance were measured at 650 nm in UV spectrophotometer. [28] Cloud point determination…”

Development and optimization of self microemulsifying drug delivery of domperidone

“…Emulsification time was measured by visual observation and percent transmittance was measured at 650 nm through UV spectrophotometer (Trull et al, 1994) • Droplet size Hundred milligram of each formulation was introduced into 100 mL of 0.1 N HCl at 25 °C and the contents were gently stirred using a propeller stirrer. The droplet size of the resultant emulsion was determined by photon correlation spectroscopy using a Mastersizer 94 2000 (Malvern Instruments, UK) which can measure sizes between 10 and 5000 nm (Patil, Joshi, Paradkar, 2004).…”