Alverine citrate is a
spasmolytic commonly prescribed in conditions such as
irritable bowel syndrome, painful
diverticular disease of the colon, and primary
dysmenorrhea. While clinical efficacy data on
alverine alone or in combination with
simethicone is freely available, surprisingly little information regarding the pharmacokinetics and metabolism of
alverine can be found in literature. The first HPLC-MS/MS analytical protocol for determination of
alverine parent, 4-hydroxy
alverine, N-desethyl
alverine and 4-hydroxy
alverine glucuronide in human plasma was developed and validated. The two validated methods were used for analyzing plasma samples collected during an open label, non-comparative, single dose, one-period, one-treatment, pharmacokinetic and metabolic profile study of Spasmonal® Forte 120 mg hard
capsule, conducted in 12 fasting healthy male and female volunteers of Caucasian descent. The study confirmed previous suspicions that parent
alverine is subject to high pharmacokinetic variability and also revealed that the metabolic process most susceptible to outlying performance in Caucasians is hydroxylation to the active metabolite 4-hydroxy
alverine. Another interesting observation made is that
alverine parent accounts for only 3%, whereas total 4-hydroxy
alverine (free and conjugated) accounts for 94% of
alverine-related moieties in circulation (based on comparisons of total exposure).