390 HEPAT ciJ720
Letter
to the Editor
___.
Changes in the plasma clearance of antipyrine after treatment healthy male volunteers with epomediol Epomediol is a terpenic alcohol which gains access into bile as a glucuronic ether (1) able to promote an osmotic choleresis in the rat (Z-3). We investigated the effect of epomedioi in man by the disappearance of aotipyrine from blood. Twenty-two healthy male volunteers (age 21-34 yr; bodv weieht 53-72 ke) entered the studv. Written mnsent was obtained from all participants. The tests were repeafed with 200 and 1OMl mg oral loads of antipyrine (in isotonic solution) after treatment with placebo or different dosages of epomediol(2 weeks treatment with 400 or 1200 mg per day). The sequence was rddomized in order to minimize periodic effects. The tea ‘.+a SfaRed at 7.30 a.m., 8-12 h after the last dose of epomediol. The timing
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of blood collection, handling of samples and the analytical procedures were performed according to previous reparts (4-5). All samples were processed in duplicate and the analytical variation ranged from 0.5-7%. Phenacetin was used as an internal standard for the HPLC separation. The pretrealment of volunteers for 2 weeks with epomedial produced, in general, a more rapid disappearance of wtipyrine from the blood. The pharmacokinetic parameters relative to the studied volunteers are sommarized in Table 1. The percentage variation belween the psrameters of plasma clearance after epomediol and the basal plasma clearance were calculated for the volunteers in whom the three tests were done. The intta-subject variation was evaluated by a r-tes‘ for paired data. For both loadings of antipyrine there is an increase in the velocity of disappearance from blood depending on the dose of epomediol.
of
Percent variation in the elimination coosfant (8) was 20.8% f 1.2 (p 4 0.001) and 36.8% +_ 1.6 (p < 0.001) higher when the clearance of 200 mg antipyrine was studied after 400 and l2OO mg epomediol (N = g), respectively, and compared to the placebo. At the same time the clearance (Cls) was increased by 25.1% f 0.8 @ < 0.001) and by 44.8% ?I 3.2 (p < 0.01) as compared to the basal kinetic When the study was performed with loDo mg antipyrine the elimination constant(B) was 23.9% + 1.2 @ < 0.001) and 68.0% f 3.5 (p c 0.001) higher after400and 12Mlmg epomediol. respectively. (N = 7) and compared to the placebo. The clearance (Cls) was at the same time increased by 28.4% + 1.5 @ < 0.001) and 53.8% t 2., (,I
Letter
to the Editor
___.
Changes in the plasma clearance of antipyrine after treatment healthy male volunteers with epomediol Epomediol is a terpenic alcohol which gains access into bile as a glucuronic ether (1) able to promote an osmotic choleresis in the rat (Z-3). We investigated the effect of epomedioi in man by the disappearance of aotipyrine from blood. Twenty-two healthy male volunteers (age 21-34 yr; bodv weieht 53-72 ke) entered the studv. Written mnsent was obtained from all participants. The tests were repeafed with 200 and 1OMl mg oral loads of antipyrine (in isotonic solution) after treatment with placebo or different dosages of epomediol(2 weeks treatment with 400 or 1200 mg per day). The sequence was rddomized in order to minimize periodic effects. The tea ‘.+a SfaRed at 7.30 a.m., 8-12 h after the last dose of epomediol. The timing
”
-.
of blood collection, handling of samples and the analytical procedures were performed according to previous reparts (4-5). All samples were processed in duplicate and the analytical variation ranged from 0.5-7%. Phenacetin was used as an internal standard for the HPLC separation. The pretrealment of volunteers for 2 weeks with epomedial produced, in general, a more rapid disappearance of wtipyrine from the blood. The pharmacokinetic parameters relative to the studied volunteers are sommarized in Table 1. The percentage variation belween the psrameters of plasma clearance after epomediol and the basal plasma clearance were calculated for the volunteers in whom the three tests were done. The intta-subject variation was evaluated by a r-tes‘ for paired data. For both loadings of antipyrine there is an increase in the velocity of disappearance from blood depending on the dose of epomediol.
of
Percent variation in the elimination coosfant (8) was 20.8% f 1.2 (p 4 0.001) and 36.8% +_ 1.6 (p < 0.001) higher when the clearance of 200 mg antipyrine was studied after 400 and l2OO mg epomediol (N = g), respectively, and compared to the placebo. At the same time the clearance (Cls) was increased by 25.1% f 0.8 @ < 0.001) and by 44.8% ?I 3.2 (p < 0.01) as compared to the basal kinetic When the study was performed with loDo mg antipyrine the elimination constant(B) was 23.9% + 1.2 @ < 0.001) and 68.0% f 3.5 (p c 0.001) higher after400and 12Mlmg epomediol. respectively. (N = 7) and compared to the placebo. The clearance (Cls) was at the same time increased by 28.4% + 1.5 @ < 0.001) and 53.8% t 2., (,I
