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Biomedical subjects

R J Ptachcinski

Publications and source records attributed to R J Ptachcinski.

At least 37 records · Page 2Linked to original sources
PubMed1986

Antipyrine kinetics in liver disease and liver transplantation.

Antipyrine kinetics were studied in seven normal subjects, 10 patients with liver disease, and 13 clinically stable patients who received a liver transplant. Five patients were studied both before and after liver transplantation. Antipyrine concentrations in saliva after oral dosing were measured by HPLC. The antipyrine t1/2 was significantly longer (P less than 0.05) in patients with liver disease than in patients undergoing liver transplantation and normal subjects. Antipyrine clearance was not significantly different between patients undergoing liver transplantation and normal subjects, but it was significantly reduced (P less than 0.05) in patients with liver disease. In five patients who were studied before and after liver transplantation, there was a significant (P less than 0.05) increase in the antipyrine clearance and a marked reduction in its t1/2 after liver transplantation. These results indicate that liver transplantation improves the drug metabolizing ability of patients with liver disease and that the oxidative metabolizing capacity of the liver in clinically stable patients after liver transplantation is similar to that of normal subjects.

Administration, Oral↗
PubMed1986

Cyclosporine pharmacokinetic profiles in liver, heart, and kidney transplant patients as determined by high-performance liquid chromatography.

Cs pharmacokinetic profiles using HPLC have aided in predicting necessary dosage alterations for specific groups of transplant patients. Additional information has been gained by HPLC profiles in nontransplant subjects who are healthy or have a stable disease state. The clinician now knows that liver disease not only impairs Cs elimination but may also have a pronounced effect upon drug absorption. While the cardiac failure patient may have reversible inhibition of Cs clearance, other factors may affect the distribution of the drug to lower dosage requirements. Impaired renal function is not an impediment to Cs elimination, but malabsorption similar to that observed in liver and bone marrow transplant patients may still occasionally complicate therapy. Pharmacokinetic information on Cs must be integrated into the complex care plan of a transplant patient to optimally utilize and monitor this pharmacologic agent.

Adult↗
PubMed1986

Cyclosporine trough concentration monitoring in liver transplant patients.

Trough blood or plasma concentration measurements of CsA must be carefully interpreted in OLT patients in relation to hepatic function, sample timing, assay specificity, and concurrent drug therapy. The RIA:HPLC ratio of blood or plasma measurements will vary with the patient's liver function, the time of blood sampling in reference to the time of drug administration, the absolute CsA concentration, and concurrent use of drugs that may alter the metabolism of CsA. The RIA assay should be used in conjunction with HPLC for trough blood or plasma measurement during the first postoperative weeks, during periods of changing hepatic function, and during changing drug regimens. In the future, the specific measurement of active or toxic metabolites of CsA should improve trough CsA concentration monitoring in OLT patients.

Chromatography, High Pressure Liquid↗
PubMed1986

Excretion of cyclosporine and its metabolites in human bile.

Quantitative and qualitative studies of cyclosporine and its metabolites were performed on human bile from liver transplant and liver disease patients. The concentration of CsA in bile is higher in patients with normal liver function than in those with poor liver function but in neither case could account for more than 2% of an absorbed dose of CsA. Although concentrations of CsA plus metabolites in bile measured by RIA were 18 to 36 times higher than HPLC concentrations, they accounted for less than 50% of an absorbed CsA dose. By means of mass spectrometry and HPLC retention times of known metabolites, peaks equivalent to the previously isolated CsA M8, M13, M17, M1, M18, and M21 of Maurer et al were found in the ether extracts of bile. Future studies should not only concentrate on the pharmacologic and toxicologic effects of the metabolites but should also accurately quantitate these compounds in blood, plasma, urine, and bile.

Bile↗
PubMed1986

Stability and availability of cyclosporine stored in plastic syringes.

The stability and availability of cyclosporine from the oral dosage form when stored in plastic syringes were examined. Solutions of cyclosporine were stored in plastic syringes for 28 days at 25 degrees C. Half of the solutions remained in room light, and samples were obtained at 3, 6, and 12 hours and 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 days. The remaining samples were protected from light, and samples were obtained at 1, 3, 5, 7, 14, 21, and 28 days. Samples stored in plastic were compared with control solutions stored in the original amber bottle. All samples were analyzed for unchanged cyclosporine by high-pressure liquid chromatography. Cyclosporine was stable and completely available from the oral dosage form when stored in plastic syringes for up to 28 days. There was no difference in the stability of cyclosporine between the solutions exposed to room light and those protected from light. Solutions of the oral dosage form of cyclosporine may be stored in plastic syringes without protection from light for up to 28 days.

Chromatography, High Pressure Liquid↗
PubMed1986

Effect of bile on cyclosporine absorption in dogs.

Oral absorption of cyclosporine was studied in dogs with and without bile diversion. Blood and bile cyclosporine concentrations were determined by a high pressure liquid chromatographic method. The absorption of cyclosporine was significantly impaired (p less than 0.05) in dogs with bile diversion. Bile and bile salts appear to be essential for the absorption of cyclosporine.

Absorption↗
PubMed1986

Leaching of diethylhexyl phthalate from polyvinyl chloride bags into intravenous cyclosporine solution.

The release of diethylhexyl phthalate (DEHP) from flexible polyvinyl chloride containers into intravenous cyclosporine solutions was studied. Intravenous cyclosporine solution or solutions containing the vehicle Cremophor EL and alcohol in dextrose were prepared in an all-glass system and stored in polyvinyl chloride (PVC) bags. Four samples were obtained at different time intervals, and DEHP content was analyzed by gas chromatography. The amount of DEHP that was leached into solutions stored in the PVC bags increased as storage time increased. By 48 hours, nearly 33 mg of DEHP had leached into the solution. Intravenous cyclosporine solutions should be prepared in glass containers to minimize patient exposure to DEHP. If plastic bags are used for preparing cyclosporine injections, the injections must be used immediately after preparation.

Cyclosporins↗
PubMed1986

Stability and availability of cyclosporine in 5% dextrose injection or 0.9% sodium chloride injection.

The stability of cyclosporine in commonly used i.v. solutions and the percentage of the drug delivered via polyvinyl chloride administration tubing were studied. Cyclosporine injection was prepared according to the manufacturer's instructions and diluted with 5% dextrose injection (D5W) or with 0.9% sodium chloride injection (NS). Admixtures containing cyclosporine 2 mg/mL were prepared in polyvinyl chloride minibags (five for each solution) and in glass containers (three for each solution). The sample obtained at time zero from a glass container protected from light was the control. Additional samples were prepared in minibags and run through 70-inch polyvinyl chloride administration sets. An HPLC assay for cyclosporine was used. Exposure to room light did not significantly affect cyclosporine concentrations. More than 90% of the initial drug concentration remained after 24 hours under all storage conditions, but less than 95% remained after 6 hours in samples diluted with NS and stored in plastic. At times up to 60 minutes, cyclosporine concentrations were significantly different in solutions infused from the minibags through polyvinyl chloride tubing from those in control solutions. Under these conditions, cyclosporine is stable in D5W in glass containers or polyvinyl chloride minibags for 24 hours and in NS for 6 hours (polyvinyl chloride) to 12 hours (glass). However, because of the potential for leaching of plasticizers, cyclosporine admixtures should be stored in glass or used within six hours if stored in polyvinyl chloride minibags. Approximately 10% of the initial drug concentration is lost to 70-inch length polyvinyl chloride infusion tubing.

Adsorption↗
PubMed1985

Cyclosporine kinetics in renal transplantation.

The pharmacokinetics of cyclosporine were evaluated in 41 recipients of a cadaveric renal transplant. Cyclosporine was taken by mouth (mean dose 14 mg/kg) on one study day and was intravenously infused over 2 hours (mean dose 4.7 mg/kg) on the next study day. Cyclosporine was extracted from whole blood and analyzed by HPLC. After intravenous infusion, cyclosporine exhibited multicompartmental behavior. The mean (+/- SD) terminal disposition rate constant was 0.065 +/- 0.036 hours-1 and the harmonic mean t 1/2 was 10.7 hours. The harmonic mean total body clearance of cyclosporine was 5.73 ml/min/kg and the mean apparent volume of distribution was 4.5 +/- 3.6 L/kg. The absorption of oral cyclosporine was slow and incomplete. Peak blood cyclosporine concentrations (means = 1,103 ng/ml) were reached between 1 and 8 hours after oral dosing (means = 4 hours). The mean relative bioavailability was 27.6% +/- 20%. Oral bioavailability was less than 10% in 17% of our subjects. The absorption and clearance of cyclosporine were highly variable. We conclude that the variability in the kinetics of cyclosporine makes trough blood level monitoring essential in the management of patients who receive renal transplants.

Absorption↗
PubMed1985

The effect of food on cyclosporine absorption.

The effect of food on the absorption of cyclosporine was evaluated in 18 recipients of cadaveric renal transplants. Cyclosporine was administered orally with a standard hospital breakfast on one study day and without breakfast on the alternate study day. The oral absorption rate as measured by the observed time to peak concentration was not significantly altered by food. The administration of cyclosporine with food resulted in a significant increase in the peak (1465 ng/ml versus 1120 ng/ml) and trough (267 ng/ml versus 228 ng/ml) blood concentrations as well as the area under the blood concentration versus time curve (11430 ng . hr/ml versus 7881 ng . hr/ml). The mean increase in area under the blood concentration versus time curve was 60.6%. The exact mechanism by which food increases the absorption of cyclosporine is not known. Regardless of the mechanism involved, if adequate immunosuppression is achieved with lower doses of cyclosporine taken with food, significant cost savings could be realized.

Absorption↗
PubMed1985

Cyclosporine.

Cyclosporine is an immunosuppressant used to prevent the rejection of transplanted kidneys, hearts, and livers. Cyclosporine suppresses T-lymphocyte function without causing myelosuppression, and its pharmacokinetics are highly variable. Compared with conventional immunosuppressive drug therapy, both patient and graft survival improved in patients treated with cyclosporine. Patients treated with cyclosporine also had less complicated hospital courses than patients receiving conventional immunosuppressants. The adverse effects from cyclosporine are reversible but include nephrotoxicity, hepatotoxicity, malignancies, hirsutism, and minor neurologic complications. Intravenous cyclosporine doses range from 2-9 mg/kg/d and oral doses range from 10-50 mg/kg/d; the dosage should be individualized based on the clinical status of the patient as well as blood concentrations of the drug. Monitoring cyclosporine blood concentrations is necessary in the postoperative management of transplant patients. Cyclosporine has contributed to the improved success of transplantation and the recognition of transplantation as a new therapeutic option for several diseases.

Animals↗