Comparison of two cyclosporine formulations in healthy Middle Eastern volunteers: bioequivalence of the new Sigmasporin Microoral and Sandimmun Neoral.
A study was conducted to establish bioequivalence between two oral cyclosporine 100 mg capsules, Sigmasporin Microoral (Gulf Pharmaceutical Industries - Julphar, United Arab Emirates, under technical co-operation with Sigma Pharma, Brazil) and Sandimmun Neoral (Novartis, Switzerland), in a Middle Eastern population, even though both formulations were found to be bioequivalent earlier in a Brazilian population (data on file). It was designed as a randomized, open label, two-way crossover study in which 30 fasting, healthy male volunteers received a single 100 mg cyclosporine dose with 240 ml of water on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 24 h. Plasma was analyzed for cyclosporine A by a sensitive, reproducible and accurate HPLC method with MS detection capable of detecting cyclosporine A in the range of 5-400 ng/ml with a limit of quantitation of 5 ng/ml. Various pharmacokinetic parameters including AUC(0-t), AUC(0- proportional, variant ), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations of both formulations. AUC(0-t), AUC(0- proportional, variant ), and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals (82.98-110.57% for AUC(0-t), 81.57-124.71% for AUC(0- proportional, variant ), 80.15-98.91% for C(max)) for these parameters were found to be within the bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Sigmasporin Microoral is bioequivalent to Sandimmun Neoral.
Najib
Naji M
NM
International Pharmaceutical Research Centre (IPRC), Amman, Jordan.
Idkaidek
Nasir
N
Adel
Ayman
A
Mohammed
B
B
Al-Masri
Sahar
S
Admour
Isra'
I
Alam
S Mahmood
SM
Dham
Ruwayda
R
Qumaruzaman
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency; D013997:Time Factors
D002214:Capsules; D016572:Cyclosporine