Six-month clinical outcome of cyclosporine microemulsion formulation (Sigmasporin Microral) in stable renal transplant patients previously maintained on sandimmun neoral.

The trial objective was to investigate the feasibility and safety of conversion to a generic microemulsion cyclosporine in stable renal transplant patients premaintained on Neoral. We enrolled 75 patients from seven centers in five Middle Eastern countries monitored them for 6 months after conversion to Sigmasporin Microral. Readings at 0, 0.5, 1, 2, 3, 4.5, and 6 months included cyclosporine blood level, serum creatinine, liver enzymes, lipid profile, blood sugar, blood pressure and adverse events. Patients included 54 men and 21 women of mean age 38.9 +/- 10.7 years at 30.3 +/- 29.3 months post-transplantation maintained on Sigmasporin Microral dose of 2.8 +/- 1.0 mg/kg per day; they were observed to be stable throughout the study period as reflected by the therapeutic blood C0 level of 181.6 +/- 102.1 and C2 of 759.2 +/- 384.4. Their absorption profile as represented by C2/C0 was 4.9 +/- 2.8, and C2/cyclosporine dose of 282.3 +/- 128.8. An average serum creatinine level of 116.1 +/- 29.5 micromol/L denoted stable graft function and their liver enzymes did not change during the study. No new-onset cases of hypertension, diabetes mellitus, or hyperlipidemia were reported among the patients. Graft function was stable for all patients, except for two incidences of mild acute rejection and two of mild cyclosporine nephrotoxicity; graft and patient survival rates were both 100%. Results of this 6-month study showed that Sigmasporin Microral was effective to maintain stable renal function in kidney transplant patients converted from Neoral with similar safety and tolerability profiles as those reported in the literature.

Therapeutic equivalence and mg:mg switch ability of a generic cyclosporine microemulsion formulation (Sigmasporin Microral) in stable renal transplant patients maintained on Sandimmun Neoral.

We tested a hypothesized pharmacokinetic difference between the reference (Sandimmun Neoral) and test (Sigmasporin Microral) products to prove therapeutic equivalence in an open, multiple fixed dose, one-way crossover, multicenter, and multinational study over a period of 29 days. Forty two stable renal transplant recipients maintained on Sandimmun Neoral were enrolled. Whole blood was collected at day 14 of the study at 0, 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after reference dosing and the same schedule was repeated at day 29 after switching on an mg:mg basis to the test product at day 15 of the study. Analysis of variance was performed for the pharmacokinetic parameters (area under the curve [AUC]0-12, maximum concentration [Cmax]) of cyclosporine using log-transformed values. Tolerability was assessed by vital signs, adverse events, and laboratory investigations. The 90% confidence interval (CI) test for the Ln-transformed, pharmacokinetic parameters was all within the US Food and Drug Administration acceptable range of 80% to 125%, as Ln area under the steady-state curve (AUCss) was within the range of 92.56 to 103.55 and Ln Cmax was within the range of 85.73 to 103.58; the same also applied for AUC0-4, which may be considered the area of greatest inter- and intra-patient variability. Furthermore, in line with the newly adopted recommendations of the Expert Advisory Committee on Bioavailability and Bioequivalence of Health Canada, the 90% CI for AUCss was within the narrow range of 90% to 112%. No significant difference in tolerability was recorded between the two products. Sigmasporin Microral (Julphar) was found to be bioequivalent and clinically interchangeable on an mg:mg basis with Sandimmun Neoral (Novartis).

Role of mebo (moist exposed burn ointment) in the treatment of fournier's gangrene.

Objectives. Fournier's gangrene (FG), though rare, is a life-threatening extensive fulminant infection of the genitals, perineum, or abdominal wall caused by a mixture of aerobic and anaerobic micro-organisms. Early and aggressive surgical debridement of the necrotic tissue and complete antibiotic coverage are the gold standards in treating FG. The purpose of our study was to assess the role of MEBO (moist exposed burn ointment) in topical treatment of the wound secondary to surgical debridement. Methods. Eleven patients (age range, 40-75 yr; mean, 55 yr) were admitted to the clinical facilities of the Department of Urology at Al Sabah Hospital, Kuwait, suffering from Fournier's gangrene, in the 31-month period between January 2004 and July 2006. All these patients were treated with broad-spectrum triple antimicrobial therapy as well as extensive debridement of necrotic tissue. The resultant wounds were treated with MEBO in six randomly selected patients and with a placebo in the remaining five patients. Results. The duration of hospital stay was reduced by 41.7% in the MEBO-treated group (30.0 vs 51.5 days) and pain control of pain was faster, which could be attributed to the faster control of infection and wound healing in this group. Conclusion. A combination of appropriate antibiotic coverage and aggressive surgical therapy is mandatory for the treatment of FG. MEBO promotes the healing of the resulting, quite extensive wound, reducing pain and controlling infection. It is a also a cost-effective therapy as it accelerates healing and reduces hospital stay by 41.7%.

Importance of Helicobacter pylori eradcation for maintenance of remission of drug associated peptic ulcer disease.

BACKGROUND: The role of Helicobacter pylori (H. pylori) eradication in non-steroidal anti inflammatory drug (NSAID) users with peptic ulcer disease is controversial especially in countries with a high prevalence of the infection. Furthermore the value of low dose omeprazole for maintenance of remission is not yet known. PATIENTS AND METHODS: 138 symptomatic out-patients receiving continuous COX 1 NSAID therapy, were treated with omeprazole 40 mg/day upon endoscopic confirmation of gastro-duodenal ulceration or erosions while those infected with H. pylori received in addition clarithromycin 500 mg and amoxycillin 1000 mg twice daily during the first week of treatment. After endoscopic confirmation of healing at the end of week 5, the patients were randomized to receive omeprazole 10 mg (n=50) or 20 mg once daily (n=66) and endoscopy repeated after 20 weeks. RESULTS: The overall healing rate (per protocol) at five weeks (116/128) was 90.6% while in 85.5% (65/76) eradication was successful. The healing rate for the H. pylori eradicated patients (58/65) was 89.2%. For those who failed eradication (8/11) it was 72.7% (NS), while for patients not infected with H. pylori at entry to the study (50/52) it was 96.2% (NS). An intention to treat analysis showed that after 20 weeks of omeprazole prophylaxis with the 10mg dose 86% (43/50) had maintained healing while for the 20mg dose a similar figure was observed (87.9; 58/66). Only three patients in the two groups (pp) had persistent H. pylori infection, all of whom relapsed. No patients discontinued treatment because of adverse effects of the drugs. CONCLUSION: H. pylori eradication was not associated with impaired ulcer healing in a Middle Eastern population with symptomatic NSAID induced gastro/duodenal lesions, when a high healing dose of omeprazole (40 mg) was used. After eradication, omeprazole 10 or 20 mg per day were highly and equally effective for maintenance of gastroduodenal mucosal integrity during continued NSAID use. H. pylori should be eradicated from symptomatic Middle Eastern NSAID users with peptic ulcer disease.

The new rHuEPO alpha (epotin) in the management of anemia of end-stage renal disease in patients on maintenance hemodialysis.

Recombinant human erythropoietin has proved to be effective to treat anemia of end-stage renal disease (ESRD). The aim of this study was to assess the efficacy and safety profile of Epotin, a rHuEPO produced in the Middle East. One hundred thirty patients with Hct

Bioequivalence of two brands of ciprofloxacin 750 mg tablets (Sarf and Ciprobay) in healthy human volunteers.

An open, randomized, two-way crossover study was carried out in 28 healthy volunteers at Gulf Pharmaceutical Industries (Julphar), as a joint venture with Saqr Hospital, Ras Al-Khaimah, UAE. The two commercial brands used were Sarf (Julphar, UAE) as test and Ciprobay (Bayer AG, Germany) as reference product. The drug was administered to each subject with 240 mL of water after an overnight fasting in two treatment days separated by a one-week washout period. After dosing, serial blood samples were collected for a period of 24 hr and serum was separated and analyzed for ciprofloxacin using a sensitive, reproducible, and accurate high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, t1/2, and lambdaz, were determined from ciprofloxacin serum concentration-time profiles for both formulations and found to be in good agreement with reported values. The parameters AUC0-t, AUC0-infinity, and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on analysis of variance (ANOVA); the 90% confidence intervals (95.73-107.62%, 94.98-108.26%, 92.80-103.90% for AUC0-t, AUC0-infinity, Cmax, respectively) for the test/reference ratios of these parameters were within the bioequivalence acceptance range of 80-125%. Based on this data, it is concluded that both formulations are bioequivalent and are interchangeable in medical practice.

Bioequivalence assessment of Azomycin (Julphar, UAE) as compared to Zithromax (Pfizer, USA)--two brands of azithromycin--in healthy human volunteers.

Two studies have been performed to assess the relative bioavailability of Azomycin (Julphar, UAE) as compared with Zithromax (Pfizer, USA) at the International Pharmaceutical Research Center (IPRC), Amman, Jordan. One study involved Azomycin capsules and the other Azomycin suspension. Each study enrolled 24 volunteers and in both studies, after an overnight fasting, the two brands of azithromycin were administered as single dose on two treatment days separated by a 2 weeks washout period. After dosing, serial blood samples were collected for a period of 192 h. Plasma harvested from blood, was analysed for azithromycin by HPLC coupled with electrochemical detection. Various pharmacokinetic parameters including AUC(0-t,) AUC(0-infinity,) C(max), T(max), T(1/2) and K(elm) were determined from plasma concentrations for both formulations and found to be in good agreement with the reported values. AUC(0-t), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals for the test/reference ratios of these parameters were found within the bioequivalence acceptance range of 80-125%. Based on these statistical inferences it was concluded that Azomycin capsule is bioequivalent to Zithromax capsule and Azomycin suspension is bioequivalent to Zithromax suspension.

Bioequivalence evaluation of two brands of cefaclor 500 mg capsules: quantification of cefaclor using solid phase extraction technique.

OBJECTIVE: To assess the bioequivalence of two cefaclor 500 mg capsule formulations, and to develop a new high performance liquid chromatographic (HPLC) method using solid phase extraction technique for the quantification of cefaclor in human plasma. METHOD: An open, randomized, two-way, crossover trial with a one-week washout period in 25 healthy volunteers. The two commercial brands used were Recocef(Julphar, United Arab Emirates) as test and Ceclor(Eli Lilly, UK) as reference product. The drug was administered with 240 mL of water after a 10-h overnight fast. After dosing, serial blood samples were collected for a period of 8 h. Plasma harvested from blood was analysed for cefaclor by a new HPLC method using a solid phase extraction technique. The limit of detection of cefaclor was 17.6 ng/mL; average recovery was 96.5%; the intraday CV was less than 8% and interday CV was less than 13%. Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, T1/2, and Kel, were determined from plasma concentrations for both formulations. Statistical analysis (ANOVA and 90% confidence intervals) were applied to AUC0-t, AUC0-infinity and Cmax for bioequivalence evaluation of two brands. The new HPLC method with solid phase extraction circumvented the problem of mixed polarity of cefaclor and facilitated its extraction from the complex plasma matrix while keeping the background free from interference due to endogenous plasma compounds. RESULTS: No significant difference was observed between the two brands of cefaclor capsules. CONCLUSION: Recocef was judged bioequivalent to Ceclor and the two products can therefore be considered to be interchangeable in medical practice.

Bioequivalence evaluation of lansoprazole 30-mg capsules (Lanfast and Lanzor) in healthy volunteers.

The bioequivalence of two lansoprazole 30-mg capsules was determined in healthy human, adult volunteers after a single dose in a randomized cross-over study. The study was conducted at Pharmaconsult, Flemington Pharmaceutical Corp., New Jersey, USA. Reference (Lanzor, Laboratoires Houde, Paris, France) and test (Lanfast, Julphar, UAE) were administered to volunteers with 240 ml water after overnight fasting. Blood samples were collected at specified time intervals, plasma was separated and analyzed for lansoprazole using a validated HPLC method. The pharmacokinetic parameters AUC(0-t), AUC(0-~), C(max), T(max), T(1/2) and elimination rate constant were determined from plasma concentration-time profile of both formulations and found to be in good agreement with previously reported values. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by the Food and Drug Administration. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range (80-120%) for bioequivalence. Based on these statistical inferences it was concluded that the two formulations exhibited comparable pharmacokinetic profiles and that Julphar's Lanfast is bioequivalent to Lanzor of Lab. Houde.

Bioequivalence evaluation of norfloxacin 400 mg tablets (Uroxin and Noroxin) in healthy human volunteers.

A bioequivalence study of two oral formulations of 400 mg norfloxacin was carried out in 18 healthy volunteers according to a single dose, two-sequence, cross-over randomized design at College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, jointly with King Khalid University Hospital. The two formulations were: Uroxin (Julphar, United Arab Emirates) as test and Noroxin (Merck Sharpe & Dohme, BV, Netherlands). Both test and reference formulations were administered to each subject after an overnight fasting on 2 treatment days separated by 1 week wash-out period. After dosing, serial blood samples were collected for a period of 24 h. Plasma harvested from blood, was analysed for norfloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2), and K(el) were determined from plasma concentrations for both the formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-infinity), and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval for test/reference ratio of these parameters were found within a bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Uroxin is bioequivalent to Noroxin.

Bioequivalence evaluation of two brands of cefuroxime 500 mg tablets (Cefuzime and Zinnat) in healthy human volunteers.

A bioequivalence study of two oral formulations of 500 mg cefuroxime axetil was carried out in 24 healthy volunteers following a single dose, standard two-treatment cross-over design at the College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, working jointly with King Khalid University Hospital. The two formulations used were Cefuzime (Julphar, United Arab Emirates) as the test and Zinnat (Glaxo Wellcome, England) as the reference product. Both test and reference tablets were administered to each subject after an overnight fasting on two treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 8 h. Plasma harvested from blood was analysed for cefuroxime by a sensitive, reproducible and accurate high pressure liquid chromatography (HPLC) method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2) and K(el) were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on an analysis of variance (ANOVA); 90% confidence interval for test/reference ratio of these parameters were found within bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Cefuzime is bioequivalent to Zinnat.

Bioequivalence evaluation of lomefloxacin 400 mg tablets (Lomax versus Maxaquin in healthy human volunteers.

This study represents the results of a randomized, single dose, two-treatment, two-period crossover study in 18 healthy male volunteers to assess the bioequivalence of two tablets of 400 mg lomefloxacin. The two formulations were: Lomax(R) (Julphar, United Arab Emirates) as the test formulation and Maxaquin(R) (Searle, S.A., UK) as the reference formulation. The study was conducted at the College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, jointly with King Khalid University Hospital, Riyadh, Saudi Arabia. After overnight fasting the two products were administered as a single dose on two treatment days separated by a 1 week washout period. Serial blood samples were collected thereafter, for a period of 48 h. Plasma harvested from blood was analysed for lomefloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max,) T(max), T(1/2), K(elm) and C(max)/AUC(0-infinity) were determined from plasma concentrations for both formulations and found to be in good agreement with reported values. Statistical modules applied to AUC(0-t), AUC(0-infinity) and C(max) revealed no significant difference in the two tested products. Based on these statistical inferences it was concluded that Lomax(R) is bioequivalent to Maxaquin(R).