Stability issues of mycophenolic Acid in plasma: from patient to laboratory.

Although mycophenolate is widely prescribed in India, therapeutic drug monitoring of mycophenolic acid is not performed in most centers. This could be due to many factors such as the large investment and expertise required for high performance liquid chromatography, or the high costs involved as specialized refrigeration is required when transporting patient specimens to the laboratories with the facility to analyze MPA. The Clinical Pharmacology unit of the Christian Medical College Hospital routinely monitors the area under the curve of MPA. In order to determine if this unit could act as a central laboratory for MPA monitoring, the stability of MPA in plasma under a series of storage and transport conditions was assessed. The procedures involved the analysis of plasma specimens from patients on mycophenolate mofetil and blank plasma spiked with MPA reference standard. A range of low and high concentrations were separately analyzed to confirm long term and short term stability. The measured concentrations of MPA showed no significant change over 5 months when stored at -20 degrees or over five days under conditions encountered during transport.

Antimicrobial prescription patterns for common acute infections in some rural & urban health facilities of India.

BACKGROUND & OBJECTIVES: Irrational use of antimicrobials is a key factor behind rapidly spreading antimicrobial resistance in microorganisms. This study was undertaken to determine the rate and pattern of antimicrobial prescribing in patients with uncomplicated acute respiratory infections, fever and diarrhoea attending a few rural and urban health settings. METHODS: The study was done in primary and secondary health care facilities of public/government and private settings at four sites in India. Patients with fever, cough, diarrhoea or ear, nose or throat infections of < 7 days were included. Pregnant women, lactating mothers, infants, seriously ill patients and patients with bloody diarrhoea or purulent nasal or ear discharge were excluded. RESULTS: Overall antimicrobial prescription rate was 69.4 per cent (95% CI 67.1, 71.7). Wide variation was observed (Thiruvananthapuram 47.6%, Lucknow 81.8%, Chennai 73.1% and Vellore 76.5%). Physicians practicing in rural and public/government settings prescribed antimicrobials more frequently than those in urban and private settings (83.8, 81.9, 68.3 and 68.2% respectively). Antimicrobials were more frequently prescribed for patients presenting with fever. Highest rate was noticed for children aged between 6 and 18 yr. Patients of the high-income group received antimicrobials more frequently (72.7%). In both public/ government and private settings, for patients who purchased medicines, the rate was higher (82.4 and 68.9% respectively), vs. those receiving free medicines (70.2 and 46.2% respectively). Two third of all antimicrobials prescribed were penicillins and co-trimoxazole, and > 40 per cent of prescriptions from private sector were quinolones and cephalosporins. INTERPRETATION & CONCLUSIONS: Our findings showed that prescription of antimicrobials for acute respiratory infections and diarrhoea was extremely common and warrants interventional strategies.

Acenocoumarol and phenytoin toxicity in the presence of CYP2C9 mutation.

This case report describes a rare interaction between therapeutic doses of phenytoin and acenocoumarol resulting in both acute phenytoin toxicity and increased international normalized ratio (INR). Interactions between these drugs are due to the pharmacokinetics and the common metabolising pathway by hepatic cytochrome P450 isoenzyme-CYP2C9. Our patient was detected to be homozygous for CYP2C9*3 by PCR-RFLP analysis resulting in markedly decreased metabolism of both the drugs. Given that these two drugs are often given concomitantly in the medical out patient department, and that CYP2C9 polymorphisms are not uncommon, clinicians should be aware of this interaction and suspect this in patients with toxicity to these drugs.

Topical phenytoin solution for treating pressure ulcers: a prospective, randomized, double-blind clinical trial.

STUDY DESIGN: Prospective, randomized, double-blind clinical trial. OBJECTIVES: To evaluate the efficacy of topical phenytoin solution in treating pressure ulcers among patients with spinal cord disorders and to evaluate the systemic absorption of topical phenytoin. SETTING: Physical Medicine and Rehabilitation Unit, Christian Medical College, Vellore, India. METHODS: Twenty-eight patients with stage 2 pressure ulcers were randomized to receive either phenytoin solution (5 mg/ml) or normal saline dressing on their ulcers once daily for 15 days. Efficacy of the treatment was determined by assessing the reduction in Pressure Ulcer Scores for Healing (PUSH 3.0), ulcer volume and ulcer size as on day 16. Serum phenytoin concentrations were estimated to determine the systemic absorption of topical phenytoin. RESULTS: Statistically insignificant but marginally higher reduction in PUSH 3.0 scores and ulcer size were seen with topical phenytoin treatment. Systemic absorption of topical phenytoin was negligible. No adverse drug events were detected during the study. CONCLUSIONS: Phenytoin solution is a safe topical agent that accelerates healing of pressure ulcers. However, its efficacy is only slightly more than normal saline treatment.

A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent.

BACKGROUND: Therapeutic drug monitoring for mycophenolic acid (MPA) is increasingly being advocated. The present therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC).However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this sampling period? AIM: To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. SETTINGS AND DESIGN: Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paired data. MATERIALS AND METHODS: Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept were evaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the time after transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the 12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factor applied. These two AUCs were then compared. STATISTICAL ANALYSIS: Linear regression, intra-class correlations (ICC) and a two-tailed paired t-test were applied to the data. RESULTS: Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2) were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. No bias was seen with a Bland Altman plot or by calculation. CONCLUSION: For patients on Cellcept with prednisolone +/- cyclosporine the 6-hour corrected is an accurate measure of the full 12-hour AUC.

A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients.

AIM: A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease. PATIENTS AND METHODS: With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 microg/5 microL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored. RESULTS: Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US 721 dollars while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US 64 dollars. CONCLUSION: Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.