Evalutation of mycophenolic acid systemic exposure by limited sampling strategy in kidney transplant recipients receiving enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine.

BACKGROUND: Enteric-coated mycophenolate sodium (EC-MPS) and mycophenolate mofetil (MMF) are prodrugs of mycophenolic acid (MPA). Although many patients still receive MMF as an inosine monophosphate dehydrogenase inhibitor, EC-MPS could be considered a reliable alternative to MMF in the immunosuppressive protocols of kidney transplant recipients. MPA shows high pharmacokinetic variability and consequently a 12-h area under the curve (AUC(0-12)) should be used to guide the therapeutic dosage. However, patient compliance and economic costs make MPA AUC(0-12) an unpractical approach. Limited sampling strategies or predictive systemic drug exposure equation models based on limited sampling times are available only for MMF but lack for EC-MPS. METHODS: The present study enrolled 26 kidney transplant recipients receiving EC-MPS as part of their immunosuppressive therapy. Twenty-six full MPA AUC(0-12) were performed. By using multiple stepwise regression analysis, we obtained several predictive equations of MPA systemic exposure in this group of patients. The value of the selected equations was tested in a subsequently enrolled group of 26 kidney transplant recipients. RESULTS: The best equations obtained in the first group of patients were the following: 22.906 + 3.880·C(0) + 1.117·C(1) + 7.527·C(8) (r = 0.901) and 35.064 +3.784·C(0) + 1.002·C(1) + 1.192·C(2) (r = 0.846). These equation models showed an optimal agreement between the full AUCs and estimated AUCs by using the validation group of patients. CONCLUSIONS: Limited sampling strategies are useful for MPA AUC(0-12) estimation in patients receiving EC-MPS and cyclosporine. The choice of one or the other equation model depends on the pharmacokinetic characteristics of the patients, in particular the potential presence of enterohepatic recirculation.

Clinical insights by the presence of bipolar disorder in pseudohypoparathyroidism type 1A.

Pseudohypoparathyroidism type 1A and its association with bipolar disorder (BD) have never been reported so far. We report a new case with both clinical entities and discuss the potential pathophysiological mechanisms of this association (protein kinase A hypoactivation, parathyroid hormone, hypocalcemia, protein kinase C activation, vitamin D deficiency). In this patient, the correction of the underlying calcium and vitamin D deficiencies leads to a better BD outcome and lower dosage of psychopharmacological agents. The conclusions might be generalized for a better understanding and management of these conditions.

Topiramate in Alcohol Use Disorders: Review and Update.

To date, a limited number of pharmacological agents exist to treat alcohol use disorders (AUDs), and there is growing interest in new therapeutic tools. In this framework, topiramate may represent a useful treatment option, although its use is not yet approved for AUDs. The main focus of this review is to discuss all the existing data supporting the use of topiramate in AUDs, with an emphasis on the most recent and relevant clinical implications. In addition, the profile of the alcoholic patient who may benefit more from the use of topiramate is outlined. In this regard, the authors conducted a PubMed search of clinical human studies published in English using the following key words: topiramate alcohol dependence, topiramate alcohol withdrawal and topiramate alcoholism. The evidence suggests that topiramate could be an effective treatment option for the management of AUDs, while there are limited results for its use to treat alcohol withdrawal syndrome. In particular, topiramate shows a greater beneficial effect in subjects with a typology of craving characterised by drinking obsessions and automaticity of drinking. Topiramate, within the dosage range of 75-300 mg/day, could be considered as a first-line treatment option for the management of AUDs. Its use appears to be safe and well-tolerated, especially in light of very recent findings.

Absence of pharmacokinetic interference of moxifloxacin on cyclosporine and tacrolimus in kidney transplant recipients.

This study investigates the potential pharmacokinetic interactions between an antimicrobial agent, moxifloxacin, and 2 immunosuppressant drugs, cyclosporine and tacrolimus, in kidney transplant recipients. Twenty-two kidney transplant patients needing antibiotic therapy for urinary tract infections are enrolled. Eleven patients are under cyclosporine treatment and the other 11 patients are under tacrolimus treatment. Because the urinary tract infections are caused by gram-negative aerobes sensitive to moxifloxacin, this antibiotic is administered by oral route at a dose of 400 mg/d for 1 week; in each patient pharmacokinetic studies are carried out before and at the seventh day of therapy. For both immunosuppressors, none of the pharmacokinetic parameters investigated show statistically significant differences between values obtained before and during treatment with moxifloxacin. In fact, the concentration-time profiles of monoclonal cyclosporine, polyclonal cyclosporine, and tacrolimus are not significantly different before and during the antimicrobial therapy. The results of the present study rule out interference of moxifloxacin with both cyclosporine and tacrolimus kinetics and indicate that the concomitant administration of the fluoroquinolone and cyclosporine or tacrolimus does not require modifications of the dosages of 2 immunosuppressant drugs.