HOW SAFE ARE BIOEQUIVALENCE STUDIES IN HEALTHY-VOLUNTEERS

Between 1981 and 1994, 58 bioequivalence studies (b.s.) were performed in 885 healthy volunteers. 93.1 per cent were single-dose, mainly of two way cross-over design. According to ATC groups, 23 were of cardiov ascular drugs (C), 11 musculoskeletal (M), nine alimentary (A), seven urogenital (G), seven antimicrobial (J), six haematological (B), three nervous (N) and two respiratory (R), 97.2 per cent of volunteers fini shed tile studies. Out Of 25 withdrawals, 14 did it by their own will, seven were excluded because of lack lack of compliance with the proto col, one because of an adverse drug reaction (ADR) (preputial oedema), one because of intercurrent illness, and two for other objective reas ons. In 35 studies the probants have been males, in 23 both sexes. sub jects were between 18 and 40 years. 209 adverse events were reported i n 18 studies (31 per cent). From 885 volunteers that came to first ses sion at the time, 115 (13 per cent) had ADRs. The association of the d rug and ADRs was defined as probable in 91 ADRs (45.9 per cent), defin ite in 66 (33.4 per sent) and possible in 41 (20.4 per cent). 73 (63.5 per cent) volunteers had one ADR, 22 (19.1 per cent) had two and 20 ( 17.4 per cent) more than two ADRs. The majority - 117 (56 per cent) - of ADRs were mild, 78 (37.3 per cent) moderate and 14 (6.7 per cent) s evere. The most, frequent ADR was headache (22.9 per cent), followed b y nasal congestion (12.9 per cent), sweating (12.4 per cent), nausea ( 6.7 per cent), restlessness (6.7 per cent), deafness and tinnitus (6.2 per cent), change of biochemical or haematological parameters (5.3 pe r cent) and other. An unusual and rare ADR tvas impotence and preputia l oedema (two volunteers on frusemide). ALI studies of G group (7-100 per cent) had ADRs, followed by C group (5-38 per cent) and A (3-33 pe r cent). Glipizide (5 mg) had highest number of ADRs (64-30.6 per cent ), bromocriptine (10 mg) had 31 (14.8 per cent) and frusemide (500 mg) 22 (10.6 per cent), The largest number of subjects with ADRs were on frusemide (13-72 per cent), glipizide (17-68 per cent) and bromocripti ne (15-52 per cent). At a time when generic drugs are of increasing im portance, the safety of b.s. is of considerable interest. Our data con firm their safety and indicate that die majority of ADRs are mild.