The bioequivalence study of Folifer-Z®: a new formulation of sustained-release iron and zinc

• Published in: International journal of pharmaceutics Vol. 178; no. 2; pp. 171 - 181
• Main Authors: Salhab, Abdulazim S., Zmeili, Suheil M., Gharaibeh, Munir N., Elayan, Hamzeh H., Sallam, Elsayyed, Al Deleq, Suleiman
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-02-1999; Elsevier
• Subjects: Adult; Bioequivalence; Biological and medical sciences; Capsules - pharmacokinetics; Chemistry, Pharmaceutical; Cross-Over Studies; Delayed-Action Preparations - pharmacokinetics; General and cellular metabolism. Vitamins; Humans; Iron; Iron - adverse effects; Iron - blood; Male; Medical sciences; Pharmacokinetics; Pharmacology. Drug treatments; Tablets - pharmacokinetics; Therapeutic Equivalency; Zinc; Zinc - adverse effects; Zinc - blood; Iron; Bioequivalence; Pharmacokinetics; Zinc; Human; Drug combination; Iron sulfate; Healthy subject; Controlled release form; Single dose; Oral administration; Bioavailability; Dosage form; Tablet; Hard capsule; Zinc sulfate; Comparative study
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(98)00368-8

The bioequivalence of Folifer-Z® tablets, a new sustained-release iron and zinc formulation was evaluated and compared to that of Fefol-Z® capsules in 30 healthy male subjects. Each subject received a single oral dose of either product according to a randomized two-way crossover design. A washout period of 1 week was allowed after each treatment. Blood samples were obtained over a 24-h period, and iron and zinc concentrations were measured. The pharmacokinetic parameters of Folifer-Z® were
C
max (103±46.2 μg/dl),
T
max (5.93±2.94 h) and AUC
0–24 h (1937±706 μg/dl per h), whereas the corresponding Fefol-Z® values were
C
max (109±41.5 μg/dl),
T
max (6.64±2.54) and AUC
0–24 h (1865±699 μg/h per dl). Analysis of variance on log-transformed data for
C
max and AUC
0–24 h revealed lack of significant differences among the two formulations. The mean relative bioavailability of AUC
test/AUC
reference was 1.07 (90% confidence interval range: 99–115%) and for
C
max test/
C
max reference was 0.96 (90% confidence interval range: 88–105%). Regarding the zinc results, the pharmacokinetic parameters of Folifer-Z® values were
C
max (101±20.7 μg/dl),
T
max (4.86±1.53 h) and AUC
0–24 h (1944±202 μg/h per dl), while the corresponding Fefol-Z® values were
C
max (102±20.7),
T
max (4.93±1.51) and AUC
0–24 h (1953±200). Analysis of variance on log-transformed zinc data for
C
max,
T
max and AUC
0–24 h revealed lack of significant difference among the two formulations. The mean relative bioavailability of AUC
test/AUC
reference was 0.98 (90% confidence interval range; 95–101%) and for
C
max test/
C
max reference was 0.92 (90% confidence interval range: 89–96%). The results also indicate a possible inhibition of zinc absorption by iron content of both formulations. It is concluded that Folifer-Z® product is bioequivalent to Fefol-Z® product.