We studied the pharmacokinetics of amikacin in a patient with acute oliguric renal failure during continuous veno-venous hemofiltration (CVVH). The volume of distribution, terminal disposition rate constant and elimination half-life for amikacin were 27.9 L, 0.023-h−41 and 29.7 h, respectively. Total body clearance for amikacin was 10.54 ml/min and CWH clearance was 10.11 ml/min. Sieving coefficient for amikacin was 0.93 ± 0.16. Our data show that during CWH at a filtration rate of 10 ml/min, the clearance of amikacin is similar to that reported in patients with renal failure who are not being treated with CVVH. (Crit Care Med 1990; 18:675)
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.
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.
Journal Article Impact of pharmacist home visits on drug therapy Get access Michele A. Schrecengost-Kibbey, B.S.Pharm., Michele A. Schrecengost-Kibbey, B.S.Pharm. Pharmacist Rx Partners Long Term Care, Inc. (a division of UPMC Health System) 500 Old Pond Road, Suite 400 Bridgeville, PA 15017 Search for other works by this author on: Oxford Academic Google Scholar Richard J. Ptachcinski, Pharm.D., Richard J. Ptachcinski, Pharm.D. Chief Executive Officer American Pharmacotherapy, Inc. Pittsburgh, PA 15237 Search for other works by this author on: Oxford Academic Google Scholar Amy L. Tuttle, M.B.A., Amy L. Tuttle, M.B.A. Manager Living-at-Home Program UPMC Health System Pittsburgh, PA 15213 Search for other works by this author on: Oxford Academic Google Scholar Teresa P. McKaveney, B.S. Teresa P. McKaveney, B.S. Research Assistant Department of Pharmacy and Therapeutics School of Pharmacy University of Pittsburgh Pittsburgh, PA 15261 Search for other works by this author on: Oxford Academic Google Scholar American Journal of Health-System Pharmacy, Volume 59, Issue 13, 1 July 2002, Pages 1293–1294, https://doi.org/10.1093/ajhp/59.13.1293 Published: 01 July 2002
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.
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 t½ 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 (X̄ = 1,103 ng/ml) were reached between 1 and 8 hours after oral dosing (X̄ = 4 hours). The mean relative bioavailability was 27.6% ± 20%. Oral bioavailability was <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. Clinical Pharmacology and Therapeutics (1985) 38, 296–300; doi:10.1038/clpt.1985.174
