Naslov
How safe are bioequivalence studies in healthy volunteers?

Autori
Huić, Mirjana ; Vrhovac, Božidar ; Francetić, Igor ; Bakran, Ivan ; Giljanović, Sanja

Izvornik
Thérapie (0040-5957) 51 (1996); 410-413

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
bioequivalence studies, healthy volunteers, ADRs

Sažetak
Between 1981 and 1994, 58 bioequivalence studies were performed in 885 healthy volunteers. 93.1% were single-dose, mainly of 2 way cross-over design. According to ATC groups 13 were of CV drugs, 11 musculosceletal, 9 alimentary, 7 urogenital, 7 antimicrobial, 6 haematological, 3 nervous, and 2 respiratory. 97.2% of volunteers finished the studies. Out of 25 with withdrawals, 14 did it by their own will, 7 were excluded because of lack of compliance with the protocol, 1 because of ADR (preputial oedema), 1 because of intercurrent illness and 2 for other objective reasons. In 35 studies, the subjects have been males, in 23 both sexes Subjects were between 18 and 40 y. 209 adverse events were reported in 18 studies (31%). From 885 volunteers that came to 1st session at the time, 115 (13%) had ADRs. The association of the drug and ADRs was defined as probable in 91 ADRs (45.9%), definite in 66 (33.4%) and possible in 41 (20.7%). 73 (63.5%) volunteers had one ADR, 22 (19.1%) had two and 20 (17.4%) more than 2 ADRs. The majority -117 (56%) of ADR were mild, 78 (37.3%) moderate and 14 (6.7%) severe. The most frequent ADR was headache (22.9%), followed by nasal congestion (12.9%), sweating (12.4%), nausea (6.7%), restlessness (6.7%), deafness and tinnitus (6.2%), change of biochemical or haematological parameters (5.3%) and other. An unusual and rare ADR was impotence and preputial oedema (2 volunteers on furosemide). All studies of G group (7-100%) had ADRs, followed by C group (5-38%) and A (3-33%). Glipizide (5 mg) had highest NO of ADRs (64- 30.6%), bromocriptine (10 mg) had 31 (14.8%), and frusemide (500mg) 22 (10.6%). The largest No of subjects with ADRs were on frusemide (13-72%), glipizide (17-68%) and bromocriptine (15-52%). At the time when generic drugs are of increasing importance, the safety of b.s. is of considerable interest. Our data confirmed their safety and indicate that majority of ADRs are mild.

Izvorni jezik
Engleski

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