[Bio-equivalence and generic drugs. Studies of bio-equivalence. II. Special situations. Reflections on problems which may arise with drugs habitually used in neurology].
OBJECTIVE
To discuss some controversial aspects and special situations which should be considered when assessing the use of generic drugs, especially those frequently used in neurology.


METHODS
We discuss the difference between the concept of average bio-equivalence and individual bio-equivalence, and the implications the selection of one or other criterion may have in the treatment of individual patients with carbamazepine. We also discuss the peculiarities and problems concerning bio-equivalence in the case of drugs with non-linear pharmacokinetics, controlled-release formulations, racemic drugs with two or more stereo-isomers and when there are differences in the excipients of different formulations of the same drug.


CONCLUSIONS
There are drugs in which it may be very difficult to show the bio-equivalence of a generic formulation because of its pharmacokinetic characteristics as occurs in the case of controlled-release drugs, the presence of active metabolites or differences in their enantiomers or even due to problems with the excipients used, although if the therapeutic range is wide and these variables are controlled in the studies done, the conclusions regarding bio-equivalence may be valid.
Zapater
P
P
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Miguel Hernández, San Juan de Alicante, España.
Horga
J F
JF
D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D002220:Carbamazepine / Q000009:adverse effects / Q000493:pharmacokinetics; D004110:Diltiazem / Q000493:pharmacokinetics; D016568:Drugs, Generic / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D009462:Neurology; D009543:Nifedipine / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013810:Therapeutic Equivalency; D014700:Verapamil / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D016568:Drugs, Generic; D002220:Carbamazepine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine