Prevention of post-herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone.

BACKGROUND: Treatment of herpes zoster (HZ) includes the use of acyclovir with or without steroids. An alternative therapy is the epidural administration of local anesthetics with or without steroids. This trial compared the efficacy of these two treatment regimens in the prevention of post-herpetic neuralgia (PHN). METHODS: Six hundred adults over 55 years of age with a rash of less than 7 days duration, and severe pain due to HZ, were enrolled and randomized to receive either intravenous acyclovir (10 mg/kg three times daily) for 9 days+prednisolone (60 mg per day with progressive reduction) for 21 days, or 6-12 ml bupivacaine (0.25%) every 6-8 or 12 h+methylprednisolone 40 mg every 3-4 days by epidural catheter during a period ranging from 7 to 21 days. Efficacy was evaluated at 1, 3, 6 and 12 months. PHN was assessed as pain and/or allodynia, and "abnormal sensations" (hypoesthesia, burning, itching, etc.). Statistical analysis was performed based on the intent-to-treat population. RESULTS: In the 485 patients who completed the study, the incidence of pain after 1 year was 22.2% (51 patients of 230) after acyclovir+steroids, and 1.6% (4 patients of 255) after epidural analgesia+steroids. The incidence of abnormal sensations was 12.2% (28 patients) after acyclovir+steroids, and 4.3% (11 patients) in group B. CONCLUSIONS: Epidural administration of local anesthetic and methylprednisolone is significantly more effective in preventing PHN at 12 months compared to intravenous acyclovir and prednisolone.

Blood concentrations and clinical effect of cyclosporin in psoriasis.

After approval by the Local Ethical Committee, 60 psoriatic patients, who participated in a previous pharmacokinetic study on cyclosporin A (CsA), gave their informed consent to continue to be studied during the maintenance treatment and at withdrawal. Peak concentration (Cmax), area under the concentration-time curve (AUC), bioavailability, elimination half-life, distribution volume, and body clearance were determined at monthly check-ups, along with blood pressure, psoriasis area, severity index (PASI), and creatinine serum levels. No modifications over time of treatment were observed on kinetic parameters. At the dose of 5 mg/kg in two daily administrations, a complete remission of the disease was observed after 1 month's treatment. At withdrawal, a worsening of PASI appeared when CsA daily dose reached 2 mg/kg b.w., the mean trough levels or AUC values being, respectively, 100 and 2,200 ng/ml.hr. There was a trend for patients with hypertension and nephrotoxicity at the end of the maintenance treatment to have higher trough, Cmax, and AUC values. Furthermore, blood pressure and serum creatinine tended to correlate better with AUC and Cmax, than with trough levels.

Cyclosporin nephrotoxicity in relation to its metabolism in psoriasis.

Cyclosporine (CsA) and some of its metabolites (M9, M17, M18, M21) have been determined by means of an LC-MASS method in eight psoriatic patients developing nephrotoxicity. In comparison with a control group (15 psoriatics who after the same period of time, with the same daily dose, did not develop nephrotoxicity) they showed an increase of CsA metabolites, especially M17. Because M17 blood concentrations in the nephrotoxic group tended to be higher than in the control group from the first week of treatment we suggest that M17 might be considered a marker of ongoing nephrotoxicity.

Oral and intravenous disposition of cyclosporine in psoriatic patients.

After informed consent was obtained and with the approval of the Local Ethical Committee, cyclosporine A (CsA) kinetics was studied in 63 psoriatic patients by giving them 2.5 mg/kg CsA orally. In order to calculate oral bioavailability, F, 22 patients were given the same dose i.v. Values of the calculated kinetic parameters were oral F = 22-63%; half-life, t1/2 beta, = 11.05-13.70 h; volume of distribution, Vd, = 4.00-5.02/L/kg; total body clearance, Cl, = 4.25-4.14 ml/min/kg. The area under the blood concentration time curve was more closely related to the dose (r = 0.66) than were trough levels (r = 0.52). No significant relationship was observed between the kinetic parameters studied and the age of the patient.