The karolinska cocktail for phenotyping of five human cytochrome P450 enzymes

Christensen, Magnus; Andersson, Kjell; Dalén, Per; Mirghani, Rajaa A.; Muirhead, Gary J.; Nordmark, Anna; Tybring, Gunnel; Wahlberg, Anneli; Yaşar, Ümit; Bertilsson, Leif

doi:10.1016/s0009-9236(03)00050-x

Cited by 138 publications

(145 citation statements)

References 37 publications

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“…They refrained from alcohol, grapefruit juice during 2 days and caffeine products during 1, 5 days before the study started. The Karolinska cocktail included omeprazole 20 mg (enterotablet of Losec Mups 20 mg; Hässle, Stockholm, Sweden), losartan 25 mg, caffeine 100 mg, quinine 250 mg and debrisoquine 10 mg [21] .…”

Section: Study Subjectsmentioning

confidence: 99%

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CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

Ramsjö

Aklillu

Bohman

et al. 2010

Eur J Clin Pharmacol

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Objectives To compare CYP2C19 enzyme activity between Swedes and Koreans controlling for the effect of CYP2C19 genotype, sex, oral contraceptive use and smoking habit.Methods CYP2C19 activity was determined in 185 healthy Swedish and 150 Korean subjects as omeprazole/5-hydroxyomeprazole ratio (metabolic ratio; MR) using high-performance liquid chromatography. Genotyping was performed by PCR using Taqman assay.Results As expected, a higher incidence of poor metabolizers (PM) was found in Koreans (14%) compared to Swedes (3.8%) and the frequency of the CYP2C19*17 allele was very low in Koreans 0.3%. Among subjects homozygous for CYP2C19*1, Koreans displayed significantly lower CYP2C19 enzyme activity than Swedes (p<0.000001). Interestingly in Koreans a pronounced gender difference was apparent: females (n=24) had significantly lower MR than males (N=30) (p<0.0001) but such a gender difference was not seen among Swedes. Swedish OC users had a higher MR than non-users (p<0.00001), whereas OC was only used by one Korean. No effect of smoking was observed. ConclusionsWe find specific gender dependent effects of CYP2C19 activity in Koreans but not in Swedes. Controlling for the effect of genotype and sex, Koreans display lower CYP2C19 activity than Swedes. The genetic, epigenetic or environmental basis for this difference remains to be identified.

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Section: Study Subjectsmentioning

confidence: 99%

“…The method for measuring omeprazole and its metabolite 5-hydroxyomeprazole was described by Tybring et al [22]and modified by Christensen et al [21].…”

Section: Phenotypingmentioning

confidence: 99%

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

Ramsjö

Aklillu

Bohman

et al. 2010

Eur J Clin Pharmacol

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“…Many cocktail studies have been conducted using humans, such as the Cooperstown 5+1 cocktail [31], Karolinska cocktail [32], Inje cocktail [33], and Basal cocktail [34]. Of these cocktail methods, the Inje cocktail includes all commercially available drugs such as caffeine (human CYP1A2 substrate), losartan (human CYP2C9 substrate), omeprazole (human CYP2C19 substrate), dextromethorphan (human CYP2D6 substrate), and midazolam (human CYP3A substrate) for which the human pharmacokinetic properties are known [33].…”

Section: Introductionmentioning

confidence: 99%

Species Differences in the Pharmacokinetic Parameters of Cytochrome P450 Probe Substrates between Experimental Animals, such as Mice, Rats, Dogs, Monkeys, and Microminipigs, and Humans

S¹

2015

J Drug Metab Toxicol

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To clarify species differences in the pharmacokinetic parameters of cytochrome P450 (CYP) activities between humans and experimental animals, we assessed several CYP activities in mice, rats, dogs, monkeys, and microminipigs, using the simultaneous administration of typical human CYP substrates, such as caffeine (human CYP1A2 substrate), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A), to these animals. The intrinsic clearance (CL int ) of these 5 substrates was also examined using the liver microsomes of humans and the experimental animals. The high bioavailabilities (BAs) and low CL int values of caffeine in the experimental animals were similar to those in humans. Mice and monkeys had lower BAs and higher CL int values of losartan than those in humans. Mice, rats, and monkeys had lower BAs and higher CL int values of omeprazole than those in humans. The lowest BAs of dextromethorphan were observed in monkeys and microminipigs, and only the CL int in dogs was similar to that in humans. The BA of midazolam in microminipigs only was similar to that in humans, while the CL int values in the other animals were similar to that in humans. These results indicated that in vitro and in vivo experimental data obtained using multiple animals including microminipigs are useful for predicting human pharmacokinetics.

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“…51313011), both supplied by the Central Pharmacy, Odense University Hospital (Denmark), at 11pm on day 3. Previous studies indicate that simultaneously administrations of low doses of these two compounds do not influence the outcome of their respective metabolic ratios [22,23,24]. Morning urine was collected after a minimum of three hours.…”

Section: Study Design and Proceduresmentioning

confidence: 99%

Systemic uptake of miconazole during vaginal suppository use and effect on CYP1A2 and CYP3A4 associated enzyme activities in women

Kjærstad

Nielsen

Nøhr-Jensen

et al. 2010

Eur J Clin Pharmacol

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The karolinska cocktail for phenotyping of five human cytochrome P450 enzymes

Cited by 138 publications

References 37 publications

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

Species Differences in the Pharmacokinetic Parameters of Cytochrome P450 Probe Substrates between Experimental Animals, such as Mice, Rats, Dogs, Monkeys, and Microminipigs, and Humans

Systemic uptake of miconazole during vaginal suppository use and effect on CYP1A2 and CYP3A4 associated enzyme activities in women

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