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Biomedical subjects

D I Min

Publications and source records attributed to D I Min.

32 records · Page 2Linked to original sources
PubMed1992

Bioavailability and patient acceptance of cyclosporine soft gelatin capsules in renal allograft recipients.

OBJECTIVE: To evaluate the relative bioavailability and patient acceptance of cyclosporine (CSA) soft gelatin capsule versus oral solution in renal allograft recipients. DESIGN, SETTING, AND PATIENTS: The bioavailability of CSA capsules was compared with that of CSA solution with crossover study design in the outpatient clinic setting. Nine renal allograft recipients with stable renal function participated in this study. METHODS: CSA dose was switched from solution to capsule in each patient for seven days. At steady-state, nine blood samples were obtained over a 12-hour period from each patient on day 7 for CSA solution and on day 14 for CSA capsules. CSA blood samples were analyzed by HPLC and fluorescence polarization immunoassay (FPIA) methods. Time to peak concentration (Tmax), peak concentration (Cmax), and area under the curve (AUC) were calculated on days 7 and 14, and compared using the matched Student's t-test. Patient acceptance was evaluated by patient preference on the questionnaire. RESULTS: For CSA blood concentrations measured by HPLC assay, the Tmax, Cmax, and AUC were 3.4 +/- 1.3 h, 569 +/- 240 nmol/L, and 4659 +/- 2144 h.nmol/L (mean +/- SD), respectively, with solution and 4.2 +/- 2.1 h, 560 +/- 257 nmol/L, and 4765 +/- 1799 h.nmol/L (mean +/- SD), respectively, with capsules. These differences were not significant (p greater than 0.1). The bioavailability was not significantly different between capsules and solutions when it was measured by PFIA assay (p greater than 0.1). The mean (+/- SD) relative bioavailability of capsules compared with solution was 109 +/- 29 percent AUC (0-12 h) measured by HPLC and 111 +/- 27 percent AUC (0-12 h) measured by FPIA. All patients expressed preference for capsules over the solution. CONCLUSIONS: CSA oral soft gelatin capsule is bioequivalent to CSA oral solution and most patients preferred the capsule to the oral solution.

Administration, Oral↗
PubMed1992

Acute hepatic failure associated with oral minocycline: a case report.

A 39-year-old woman was evaluated for possible liver transplantation due to rapidly developing hepatic failure 4 weeks after initiation of oral minocycline 100 mg twice a day for the treatment of acne. The patient developed a maculopapular rash, malaise, fever, nausea, and vomiting 2 weeks prior to admission to the hospital. On admission, her symptoms rapidly progressed to liver failure characterized by rapidly rising liver enzyme levels, worsening encephalopathy, and coagulopathy. Viral hepatitis serologies and blood cultures were all negative. After intensive supportive care for 2 weeks, the patient's condition gradually improved and she was discharged with mildly elevated liver enzyme levels and pruritus, without need of liver transplantation. Minocycline-induced hepatic injury is an idiosyncratic reaction with a sensitization period that appears to be 3-4 weeks in duration. The characteristic features include rash, fever, lymphadenopathy, and eosinophilia, as well as severe alterations in liver function. The high liver enzyme levels and the significant prolongation of the prothrombin time suggest massive hepatocellular damage. In light of the profound liver damage that occurs with this adverse reaction, care should be taken in administering minocycline to patients who have concomitant liver disease. It is recommended that patients should be instructed as to the possible signs and symptoms of toxicity and be monitored for evidence of idiosyncratic reaction or liver failure.

Acne Vulgaris↗
PubMed1991

Complications associated with immunosuppressive therapy and their management.

Besides general complications of immunosuppression such as increased susceptibility to opportunistic infections or malignancy, individual immunosuppressive agents are associated with specific side effects. Nephrotoxicity is the major side effect of cyclosporine (CsA). Various attempts have been made to minimize this toxicity, such as monitoring drug blood levels, modifying the protocol, and coadministering other agents. Other side effects caused by CsA are hepatotoxicity, hyperkalemia, hypertension, tremor, gum overgrowth, and hirsutism. Azathioprine (AZA) causes dose-related bone marrow suppression, commonly leading to leukopenia. Careful monitoring of complete blood cell count and dosage adjustment according to white blood cell count are usually adequate to prevent serious leukopenia. The side effects of corticosteroids are numerous and include slow wound healing and de novo insulin-dependent diabetes mellitus. Many complications are dose related, and with low dosage or discontinuation of steroids, their frequency rapidly decreases. Antilymphoblast and antithymocyte globulins (P-ALG) are foreign antibodies and may cause allergic-type reactions such as fever, chill, and hypotension. The initial side effect of monoclonal antibody (muromonab-CD3, OKT3) is similar to that of P-ALG. It includes high fever, shaking chills, headache, rigors, and hypotension. To prevent it, acetaminophen, an antihistamine, and a steroid usually are administered before injection. Because this agent is also associated with high frequency of pulmonary edema, it should not be given to any patient who has more than 3% body weight gain during the week prior to therapy. In rare case, it causes aseptic meningitis or encephalopathy, which is manifested by fever, severe headache, and seizure.

Adrenal Cortex Hormones↗
PubMed1990

An increased incidence of late acute rejection episodes in cadaver renal allograft recipients given azathioprine, cyclosporine, and prednisone.

We studied the incidence of biopsy-proven, acute rejection episodes occurring after 1 year posttransplant in cadaver renal allograft recipients. The 328 patients evaluated were given three immunosuppressive drug protocols. Group I (transplanted 9/80-6/84) (n = 75) received azathioprine, prednisone (P), and antilymphoblast globulin; group II (transplanted 9/80-6/84) (n = 83) received cyclosporine and P; group III (transplanted 7/84-12/86) (n = 170) received ALG, AZA, CsA, and P (sequential therapy). The incidence of first acute rejection episodes occurring up to 1 year posttransplant was 55% in group I and 35% in groups II and III. The incidence of late (greater than 1 year) acute rejection episodes was 6.5% in group I, 2.5% in group II, and 9.5% in group III (group II vs. III, P = 0.02). In group III, 50% of the late rejections were first, 44% second, and 6% third. The primary etiologies of this increased incidence of late acute rejection may have included subtherapeutic CsA levels and lower P doses. Sequential immunosuppressive therapy has been shown to be advantageous in the first posttransplant year. However, unless adequate immunosuppression is maintained, this approach can be associated with a significantly increased incidence of late acute rejection.

Adult↗
PubMedDate not supplied

Evaluation of traditional African medicine "Compound R" for the treatment of thermal burn wounds in fuzzy rats.

The efficacy of an oil-in-water emulsion of a traditional Kenyan medicine, Compound R, on thermal burn wounds in fuzzy rats is reported. The burn wounds were inflicted on the depilated skin of rats with a 2 cm diameter aluminum template heated at 65 degrees C. Mean +/- SD days to healing (complete closure) were 9.9 +/- 2.2 (range 7 to 14 days) and 13.3 +/- 2.4 (range 10 to 16 days) for the treated and control (untreated) wounds, respectively (paired Student's t test, t value -5.667, p = 0.0003). Preliminary microbiologic results showed no activity of Compound R against some of the commonly encountered pathogens in burn wounds. Compound R appears to decrease the days to burn wound healing in fuzzy rats. This study provides preliminary data for further investigations of Compound R in managing burn wounds.

Administration, Topical↗
PubMedDate not supplied

Effect of erythromycin on ethanol's pharmacokinetics and perception of intoxication.

STUDY OBJECTIVE: To determine the effect of erythromycin on ethanol's pharmacokinetics and perception of intoxication. DESIGN: Double-blind, randomized, placebo-controlled, crossover study. SETTING: A clinical research center. PARTICIPANTS: Ten healthy volunteers. INTERVENTIONS: Erythromycin base 500 mg or identical placebo was administered 3 times/day for 7 days. On day 8, ethanol 0.8 g/kg was administered by mouth concurrently with erythromycin or placebo. A 2-week washout period was allowed between each treatment arm. MEASUREMENTS AND MAIN RESULTS: Twelve blood samples were obtained over a 12-hour period to determine ethanol concentrations. Perception of intoxication was determined at each time point using a 10-cm visual analog scale. Ethanol concentrations were determined using a gas chromatographic method. Mean +/- SD ethanol pharmacokinetics for erythromycin versus placebo were time to peak ethanol plasma concentrations 1.1 +/- 0.4 hours versus 1.3 +/- 0.3 hours, peak ethanol concentrations 118 +/- 18 mg/dl versus 114 +/- 27 mg/dl, ethanol oral clearance (CL/F) 2.9 +/- 0.8 ml/min/kg versus 3.4 +/- 2.2 ml/min/kg, and area under the curve 481 +/- 104 mg.hour/dl versus 465 +/- 132 mg.hour/dl (p > 0.05). The blood ethanol concentrations and perception of intoxication scores on a visual analog scale were well correlated (r2 = 0.78, p < 0.01). Mean +/- SD areas under the effect versus time curve were 35.1 +/- 20.7 cm/hour and 31.5 +/- 18.2 cm/hour for erythromycin and placebo, respectively (p > 0.05). CONCLUSION: Oral erythromycin base 1500 mg/day compared with placebo does not alter ethanol's pharmacokinetics or perception of intoxication in healthy volunteers.

Administration, Oral↗
PubMedDate not supplied

Time-dependent disposition of tacrolimus and its effect on endothelin-1 in liver allograft recipients.

STUDY OBJECTIVE: To characterize a time-dependent disposition of oral tacrolimus and its relationship with plasma endothelin-1 concentrations. DESIGN: Randomized, crossover study. SETTING: Clinical research center of a university-affiliated hospital. PATIENTS: Twelve stable liver transplant recipients. INTERVENTIONS: In the steady state, 23 blood samples were taken from each patient before and after tacrolimus administration over 24 hours. MEASUREMENTS AND MAIN RESULTS: Whole blood samples for tacrolimus and plasma endothelin-1 were analyzed by enzyme immunoassay. The relationship of their concentrations and their pharmacokinetic parameters between morning and evening doses were compared. The area under the curve (AUC) of tacrolimus in the morning dose was significantly larger than that in the evening dose (219 +/- 54 ng.hr/ml and 188 +/- 57 ng.hr/ml, respectively, p = 0.004). The mean time to peak concentration (Tmax) was significantly shorter for the morning dose than for the evening dose (1.6 +/- 0.7 hrs and 3.5 +/- 2.9 hrs, respectively, p = 0.01). The mean peak concentration (Cmax) was significantly higher in the morning dose than in the evening dose (32.2 +/- 9.1 ng/ml and 21.6 +/- 8.3 ng/ml, respectively, p = 0.008). However, the mean through concentration (Cmin) was not significantly different between doses. Endothelin-1 concentrations followed the same pattern as tacrolimus, with AUC and Cmax for the morning significantly higher than those for the evening dose of tacrolimus (AUC 13.8 +/- 3.7 pg.hr/ml, morning, and 11.0 +/- 3.5 pg.hr/ml, evening, p = 0.005; Cmax 2.4 +/- 1.1 pg/ml morning, and 1.5 +/- 0.6 pg/ml evening, p = 0.02). Tacrolimus levels did not correlate with endothelin-1 levels (r2 = 0.06, p = 0.001). CONCLUSIONS: Tacrolimus disposition in liver transplant patients is determined by time of administration. Plasma endothelin-1 concentrations follow the same pattern as blood tacrolimus concentrations.

Adult↗
PubMedDate not supplied

Cyclosporine trough concentrations in predicting allograft rejection and renal toxicity up to 12 months after renal transplantation.

STUDY OBJECTIVE: To evaluate the utility of cyclosporine (CsA) trough concentrations as a monitoring tool for acute graft rejections and CsA nephrotoxicity. DESIGN: Retrospective chart review. SETTING: University-affiliated teaching hospital. PATIENTS: One hundred thirty-seven adults who had undergone kidney transplantation. MEASUREMENTS AND MAIN RESULTS: Clinical data extracted from the charts were CsA dosage, CsA trough levels (whole blood, HPLC method), biopsy findings to confirm acute rejections, and serum creatine to determine clearance by the Jelliffe method. Data were collected at up to 1 month, between 1 month and 3 months, and between 3 and 12 months after transplantation. For each time period, receiver's operating characteristics curves were generated to identify the optimum CsA concentration for avoiding acute rejection and CsA nephrotoxicity. At up to 1 month, the CsA therapeutic response threshold was 182 ng/ml (sensitivity 69%, specificity 84%, p<0.0001) and toxicity threshold for CsA nephrotoxicity was 204 ng/ml (sensitivity 89%, specificity 56%, p<0.0001). Between 1 month and 3 months, the respective figures were 175 ng/ml (sensitivity 58%, specificity 89%, p<0.0002) and 189 ng/ml (sensitivity 87%, specificity 65%, p<0.0001). Between 3 and 12 months, the CsA therapeutic response threshold decreased to 135 ng/ml (sensitivity 56%, specificity 40%, p>0.1) and the toxicity threshold for CsA nephrotoxicity remained relatively static at 204 ng/ml (sensitivity 100%, specificity 14%, p<0.0001). CONCLUSION: Early in CsA therapy it is essential to prevent graft rejection. Drug concentrations exceeding approximately 182 ng/ml threshold accomplish this goal. Later, successful therapy demands that CsA nephrotoxicity be avoided. This goal is accomplished by not exceeding a CsA concentration of 204 ng/ml.

Adolescent↗