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Biomedical subjects

C Kroon

Publications and source records attributed to C Kroon.

11 recordsLinked to original sources
PubMed1995

A placebo-controlled parallel study of the effect of two types of coffee oil on serum lipids and transaminases: identification of chemical substances involved in the cholesterol-raising effect of coffee.

In a randomized double-blind parallel study in 36 subjects the effect on serum cholesterol of a daily dose of 2 g lipid extracted from green Arabica and Robusta coffee beans was studied. Arabica oil elevated serum total cholesterol by 1.1 mmol/L (95% CI for the difference from placebo: 0.41, 1.73 mmol/L); the effect of robusta oil (+0.5 mmol/L) was not statistically significant (95% CI: -0.01, 0.92 mmol/L). Arabica oil also raised plasma triglycerides by 0.8 mmol/L (95% CI: 0.26, 1.25 mmol/L). The effect of robusta oil on triglycerides was +0.14 mmol/L and not significant (95% CI: -0.26, 0.42 mmol/L). In the 12 subjects taking arabica oil an average serum alanine amino-transferase elevation of 18 U/L (95% CI: 9.4, 28.4 U/L) was observed. Because only arabica oil contains kahweol and arabica coffee contains more cafestol than does robusta oil, this is further evidence for the role of diterpenes in the rise of serum cholesterol and alanine aminotransferase after consumption of boiled coffee.

Administration, Oral↗
PubMed1992

Pronounced effects of the combination of a new thromboxane antagonist (GR32191) and heparin on bleeding time in man.

Potential pharmacokinetic and pharmacodynamic interactions between two oral doses of GR32191 (40 and 80 mg), a new thromboxane antagonist, and heparin (5,000 IU bolus + 1,000 IU/h for 3 h) were studied in eighteen healthy male volunteers using two separate double-blind, randomised, placebo-controlled, cross-over studies. Mean (range) bleeding time values were 8.4 min (7.5-9.7) during heparin/placebo, 12.1 min (9.2-18.6) (GR32191/placebo) and 16.3 min (11.5-21.4) (GR32191/heparin) in the 40 mg study, while these values were 8.7 min (5.5-15.5), 16.0 min (9.3 - greater than 36.0) and 23.8 min (10.7 - greater than 36.0), respectively in the 80 mg study. Compared to screening values, the combination of 80 mg of GR32191 and heparin had a greater effect on the bleeding time than the sum of the prolongations after the separate treatments (p = 0.05). In the 40 mg study this was not the case. Pharmacokinetics of heparin (as assessed by plasma anti-Xa and antithrombin activity) and GR32191 were unaltered during co-administration of the two drugs. GR32191 did not influence the effects of heparin on APTT. Heparin slightly diminished the inhibition of collagen induced platelet aggregation by 80 mg of GR32191 and the U-46619 (thromboxane A2-mimetic) induced platelet aggregation remained unchanged. Overall fibrinolytic activity (as evaluated by the fibrin plate test) was similar during all three treatments in the study with 80 mg. The combination of 80 mg of GR32191 and heparin caused a prolongation of the bleeding time which was more than expected on the basis of their individual effects.

Biphenyl Compounds↗
PubMed1992

Highly variable anticoagulant response after subcutaneous administration of high-dose (12,500 IU) heparin in patients with myocardial infarction and healthy volunteers.

BACKGROUND: In this study, the anticoagulant response of 12,500 IU heparin s.c. was investigated in patients with myocardial infarction and healthy volunteers to determine variabilities in response and modifying factors. METHODS AND RESULTS: On the fourth day after thrombolytic therapy, blood samples were taken before and at frequent intervals until 10 hours after the injection of 12,500 IU heparin s.c. Plasma anti-Xa activity, anti-IIa activity, and the activated partial thromboplastin time (APTT) were measured in addition to body weight and thickness of the abdominal subcutaneous fat layer. Contrary to expectations, the increase of anti-Xa activity, anti-IIa activity, and APTT compared with baseline (predrug) levels was very small, with an average maximal APTT of 42.6 seconds (SD, 12.4 seconds; range, 30.4-70.7 seconds). Subsequently, the influence of the length of the injection needle on the anticoagulant effect of 12,500 IU heparin s.c. was studied in 10 healthy volunteers to find a factor that could be responsible for the poor response in the patients. The length of the injection needle did not influence the anticoagulant effect of heparin. Large interindividual and intraindividual variabilities were seen in the volunteers. The majority of volunteers had minimal prolongation of the APTT, but very strong prolongation was also seen (maximal APTT, 163 seconds). There was no correlation between the abdominal skinfold thickness and anti-Xa activity, anti-IIa activity, or APTT (p > 0.05), but in the patient study, there was a correlation between weight and anti-Xa activity and anti-IIa activity (p < 0.05), and in the volunteer study, there was a correlation between weight and anti-Xa activity and APTT (p < 0.05). CONCLUSIONS: Subcutaneous administration of heparin in a fixed dose for prophylactic and therapeutic purposes may be inadequate because of the large interindividual and intraindividual variations in anticoagulant effect.

Adult↗
PubMed1991

Influence of skinfold thickness on heparin absorption.

The absorption of high and low molecular fractions of heparin from the subcutaneous compartment was evaluated in eight healthy males. They were given an intravenous infusion of 4000 U calcium heparin in 4 hours and on another occasion a subcutaneous injection of 12,500 U calcium heparin (washout period of 1 week). Anticoagulation was monitored by anti-Xa, antithrombin activity, and activated partial thromboplastin time. To evaluate factors that might influence absorption, body weight, body fat, and abdominal skinfold thickness were recorded. There was a pronounced inter-individual variability in absorption but the absorption of the two fractions of heparin was similar. The highly variable absorption was related to the abdominal skinfold thickness, and this could have implications for therapeutic and prophylactic heparin regimens.

Abdominal Muscles↗
PubMed1990

[Anaphylaxis following use of polidocanol].

Three female patients had serious anaphylactic reactions to sclerotherapy with polidocanol (Aethoxysklerol) within 15 minutes after administration for varicose veins in the legs. Two of them received the drug for the first time. The first patient developed cardiac arrest which was successfully treated. The second patient showed signs of an adult respiratory distress syndrome, while in the third the ECG was compatible with cardiac ischaemia. Recovery was complete and uneventful in all patients. The incidence of allergic reactions to polidocanol has been estimated at 1:10,000. In view of the considerable underreporting of adverse reactions we feel that the frequency of severe anaphylactic reactions to this drug may be underestimated.

Adult↗
PubMed1990

Interaction of the combined medication with the new low-molecular-weight heparinoid Lomoparan (Org 10172) and acenocoumarol.

A high intravenous dose of the low-molecular-weight heparinoid Lomoparan (Org 10172) was administered to 6 healthy males in a steady state of anticoagulation (Thrombotest) by acenocoumarol. Prothrombin time, activated partial thromboplastin time and Stypven time were prolonged to a degree which was greater than that expected on the base of the summation of the effects by each drug alone. This effect was observed for a period of up to 1 h. The Thrombotest was affected for up to 5 h after the intravenous administration of Org 10172, therefore it is deemed unsuitable for monitoring the combined effects of these two anticoagulants during this period. Acenocoumarol did not affect the pharmacokinetic parameters of Org 10172 with the exception of a slight reduction of the clearance of plasma anti-Xa activity.

Acenocoumarol↗
PubMed1990

Detection of drug interactions with single dose acenocoumarol: new screening method?

In this study, a design for the evaluation of drug interactions with an oral anticoagulant drug was investigated. The interaction between a single dose of acenocoumarol and cimetidine or pentobarbitone was studied. Nine healthy volunteers received three treatments: 1) 10 mg acenocoumarol in combination with cimetidine, 2) 10 mg acenocoumarol in combination with placebo, 3) 10 mg acenocoumarol after one week pretreatment with pentobarbitone. The pharmacokinetics and the pharmacodynamics of acenocoumarol were monitored for 36 h. In all subjects the plasma concentration of acenocoumarol remained consistently higher during cimetidine treatment and consistently lower after pentobarbitone pretreatment compared to placebo treatment. Cimetidine increased the anticoagulant response of acenocoumarol as measured by the Thrombotest and pentobarbitone decreased this response in all subjects. It is concluded from this study that both pharmacokinetic and pharmacodynamic drug interactions with acenocoumarol (and presumably other oral anticoagulants) can be detected after single doses, possibly obviating the use of long-term anticoagulation in healthy volunteers.

Acenocoumarol↗