Optimization of immunosuppression by switching from azathioprine to enteric-coated mycophenolate sodium in stable kidney transplant patients.

The aim of our retrospective, observational, single center study was to analyze renal function changes among stable kidney transplant patients treated with a calcineurin inhibitor (CNI) + azathioprine (AZA), in whom immunosuppression was optimized by a switch from AZA to enteric-coated mycophenolate sodium (EC-MPS) with a view to protecting long-term renal function. Between April 2005 and June 2008, 36 renal transplant patients on previous treatment with a CNI and AZA for a period of 86.94 +/- 66.9 months were switched to EC-MPS. After the change, there were no cases of acute rejection episodes. Six patients (16.6%) developed gastrointestinal secondary effects and 5 had to discontinue EC-MPS treatment: 4 due to severe diarrhea 1 due to thrombocytopenia. Among the remaining patients, it was possible to gradually increase the EC-MPS dose (starting at 376 +/- 122 mg/d vs current at 533.5 +/- 210 mg/d; P < .002), maintaining through levels at 2.1 +/- 1.9 ng/mL. Although 11 patients (30.5%) displayed chronic allograft nephropathy upon the preconversion biopsy, at a follow-up of 29.2 +/- 9.4 months they showed significantly improved renal function (Modification of Diet in Renal Disease [MDRD4] at change 49.5 +/- 19.8 mL/min/1.73 m(2) vs current MDRD4 55.6 +/- 23.4 mL/min/1.73 m(2); P = .02), with no increase in proteinuria (proteinuria at change 0.4 +/- 0.4 g/d vs current proteinuria 0.4 +/- 0.5 g/d; P = NS). This improvement was evident without changes in CNI levels: cyclosporine at change 133.1 +/- 30.2 ng/mL vs current 122 +/- 28 ng/mL (P = NS) and tacrolimus at change 7.7 +/- 2.2 ng/mL vs current 8.2 +/- 2.4 ng/mL (P = NS). In conclusion, conversion from AZA to EC-MPA to optimize immunosuppression seemed to be safe, with no complications in 85% of cases, as well as effective, achieving improved long-term renal function protection. These results suggested a greater protective immunological effect by switching from AZA to EC-MPA.

Effect of sodium deoxycholate on the dissolution and absorption of copper-indomethacin and zinc-indomethacin.

The effects of sodium deoxycholate on the dissolution of indomethacin metal complexes were investigated. At pH 7.2, the dissolution of copper-indomethacin was very slow, while the dissolution of zinc-indomethacin was higher but less than that of indomethacin. In the presence of 5 mg of sodium deoxycholate, the dissolution of copper-indomethacin and zinc-indomethacin was significantly enhanced. The absorption of zinc-indomethacin in the rat jejunum was low, but that of copper-indomethacin was high, as compared to indomethacin. The addition of 0.2% sodium deoxycholate significantly enhanced the jejunal absorption of zinc-indomethacin in the rat, but did not increase the absorption of copper-indomethacin. Results indicated that the in vivo absorption behavior of zinc-indomethacin was predictable by in vitro dissolution, but such correlation was not applicable to copper-indomethacin. The absorption of copper-indomethacin was similar to that of indomethacin, in spite of its poor dissolution.

Pharmacokinetics of prednisolone sodium succinate and its metabolites in normovolemic and hypovolemic dogs.

Tritium-labeled prednisolone sodium succinate was administered IV to 4 healthy, awake, nonsplenectomized dogs. The concentration of prednisolone and its metabolites in the plasma were measured for 10 hours. Forty-one percent of the blood volume of these dogs was removed, and plasma prednisolone was measured again. The data before and after hemorrhage were fitted to a 2-compartment open model. From plasma profiles, a rapid distributional phase, followed by a slower phase, was observed in control and shock groups. Volume of the central compartment of prednisolone before and after hemorrhage was 165 ml/kg of body weight and 110 ml/kg, respectively; and the difference was significant (P less than 0.05). The rate of total body clearance of prednisolone before and after hemorrhage was 3.96 ml/min/kg and 2.53 ml/min/kg, respectively; the difference was significant. The mean plasma half-lives for prednisolone sodium succinate and its metabolites, before and after hemorrhage, were 166 and 197 minutes, respectively; the difference was not significant. The mean half-life data indicated that prednisolone sodium succinate may be repeated in a patient 2.5 to 3 hours after onset of treatment if signs of hypovolemic shock reappear.

GLC determination of phenacemide in tablets.

A GLC procedure was developed for phenacemide and was shown to be less time consuming than the official assay without sacrificing accuracy. The procedure involves extraction from powdered tablets and addition of pentylenetetrazol as the internal standard. The amount of phenacemide is determined by comparison of the ratio of the area under the curves to that of a standard.

Pharmacokinetics of a single, orally administered dose of digoxin in horses.

Digoxin (elixir, 0.022 mg/kg) was administered via stomach tube to healthy horses of mixed breeding and sexes. Serum digoxin concentrations reached a peak (2.21 +/- 0.6 ng/ml) at approximately 1 hour after dosing and had a half-life of 28.8 +/- 10.7 hours. Digoxin kinetics followed a triexponential curve, indicating that at least a 2 compartmental model is required to characterize the serum concentration-time curve after this route of administration. It was calculated that to achieve average serum concentrations of 1.1 ng/ml, an oral dose of 17.4 microgram of digoxin elixir/kg/day and an IV dose of 6.1 microgram of parenteral preparation/kg/day would be required. There was no significant (P greater than 0.05) alteration in base-line serum calcium, potassium, and sodium concentrations and heart rate, P-R interval, and mean arterial blood pressure.

Benzocaine diffusion from polyethylene glycol through human stratum corneum.

The diffusion, penetration, and surface effects of benzocaine incorporated in various polyethylene glycol ointment bases through human stratum corneum were studied. Benzocaine diffusion was measured by following the benzocaine concentration in the receiving compartment of a diffusion cell. The ointment was placed in the other cell compartment and was separated from the receiving compartment by sheets of human stratum corneum. Surface effects were monitored by scanning electron micrographs of the stratum corneum. Results showed a decrease in drug diffusion in the presence of relatively high amounts of the lower molecular weight portions of polyethylene glycol. Scanning electron microscope studies showed that both benzocaine and polyethylene glycol affect the surface structure of the stratum corneum. Thermal analysis indicated that benzocaine dissolves in polyethylene glycol.

Effects of divalent cations and sodium taurocholate on pancreatic lipase activity with gum arabic-emulsified tributyrylglycerol substrates.

The effects of Ca2+ and/or sodium taurocholate on lipase activity with gum arabic-emulsified tributyrylglycerol substrates were investigated. Calcium was found to slightly increase lipase activity while bile salts showed marked inhibition except at very low concentrations. Calcium eliminated inhibition seen with low concentrations of bile salts and reduced the inhibition seen at higher bile shift of the enzyme from the alkaline region in the absence of bile salt to the slightly acidic region in the presence of bile salt. Calcium was shown to eliminate the time lag periods between enzyme addition and maximum rate of hydrolysis seen at low substrate concentrations and the time lag noted when bile salts were included with normal (substrate concentration not limiting) assay concentrations of substrate. Zeta potential measurements indicated that Ca2+ reduced the negative charge on the gum arabic-emulsified particle while bile salts did not increase the negative charge. Commercial preparations of gum arabic were found to have significant concentrations of Ca2+ and Mg2+.