Lack of effect of ponsinomycin on the pharmacokinetics of nicoumalone enantiomers.

Abstract

Pharmacokinetic interaction between ponsinomycin‐nicoumalone was studied in six subjects who received an 8 mg oral dose of racemic nicoumalone alone and 4 days into an oral regimen of ponsinomycin 800 mg twice daily. The concentrations of R(+) and S(‐)‐nicoumalone in plasma were measured using a stereospecific h.p.l.c. assay. The disposition characteristics of nicoumalone enantiomers in the control phase of this study were similar to those reported previously with the exception of the data for one subject whose oral clearance for S(‐)‐ nicoumalone was seven times lower than those in the other subjects. A statistically significant effect of ponsinomycin on the kinetics of R(+) and S(‐)‐nicoumalone was not demonstrated.

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

“…Roxithromycin [215] prolongs the tY2 of theophylline by 8%. [215] However, it has been shown that josamycin, [145,148,236] midecamycin acetate (miocamycin), [150,151] midecamycin [149] and spiramycin [152] have no influence on the pharmacokinetic profile of theophylline. Similarly, amongst the quinolones, pipemidic acid [137] and enoxacin [139,140,146,199,237] decrease the clearance of theophylline markedly by 43 to 73%, while ciprofloxacin [135,139,197] and pefloxacin [139,197] reduce this parameter by approximately 30%.…”

Altered pharmacokinetics of R - and S -acenocoumarol in a subject heterozygous for CYP2C9*3

“…The pharmacokinetics of acenocoumarol has been reported 17 , 18 , 23 , 24 , 25 . The CYP genotypes of the volunteers participating in those studies were not established.…”

“…Reported genotype distribution frequencies of CYP2C9*3 among Caucasians would predict 1 out of 6 to 8 subjects to be a carrier of the mutant allele 8 , 11 . However, only one study 24 reported on a subject (1 out of 6 participants) with a deviating S ‐acenocoumarol oral clearance (2.9 L/h vs 21.3 L/h). With hindsight, that particular subject was probably a carrier of CYP2C9*3 .…”

Effect of ponsinomycin on the pharmacokinetics of dihydroergotamine administered orally

“…Ponsinomycin is the 9,3'-diacetylmidecamycin ; it interferes with carbamazepine distribution (Couet et al, 1990), but it.demonstrated no effect on the plasma pharmacokinetics of theophylline (Principi et al, 1987;Couet et al, 1989). The effect of ponsinomycin on DHE pharmacokinetics is now being investigated following single oral administration of this ergot alkaloid in young healthy volunteers.…”