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Biomedical subjects

G Johnsson

Publications and source records attributed to G Johnsson.

At least 19 recordsLinked to original sources
PubMed1998

The interaction effect of grapefruit juice is maximal after the first glass.

OBJECTIVE: To compare the acute effect of grapefruit juice intake on the pharmacokinetics and haemodynamic effects of felodipine ER tablets with the interaction after 14 days intake of drug with juice. METHODS: Twelve healthy male volunteers were included in this cross-over trial and randomly allocated to a daily intake of a 10-mg felodipine extended release tablet with water or grapefruit juice for 14 days. The two study periods were separated by at least 14 days. The pharmacokinetics of felodipine and dehydrofelodipine, as well as the haemodynamic effects of the drug, were studied during day 1 and 14 in each period. RESULTS: Similarly to previous single-dose studies, the treatment during the first day with grapefruit juice increased the AUC (+73%) and Cmax (+138%) of felodipine when compared with the control treatment. On day 14 a similar effect of grapefruit juice was observed, with an increased AUC24 (+57%) and Cmax (+114%) of felodipine compared with the control experiment. A significant accumulation of felodipine occurred during both the control (+37%) and grapefruit juice (+25%) period. The extent of accumulation was not significantly different in the two treatment periods. The pharmacokinetics of the metabolite dehydrofelodipine were affected to a similar extent by the juice on day 1 and day 14. The first dose of felodipine together with grapefruit juice was associated with a significant additional increase in heart rate when compared with the control therapy, whereas there was no additional effect on blood pressure when therapy included grapefruit juice. On day 14 the intake of drug with juice resulted in an additional increase in heart rate and reduction in diastolic blood pressure in comparison with the control experiment. Furthermore, the vascularly related adverse events were more frequent in the period including grapefruit juice. CONCLUSION: The interaction between grapefruit juice and felodipine appears to be already fully developed after the first glass of grapefruit juice, as the change in pharmacokinetics in comparison with the control experiment is similar on day 1 and on day 14. Concomitant intake of 10 mg felodipine ER and the juice is associated with increased haemodynamic effects in healthy subjects both after a single dose and following 14 days of concomitant intake.

Adult↗
PubMed1998

A novel rapid enzyme immunoassay (Fluorophos BetaScreen) for detection of beta-lactam residues in ex-farm raw milk.

A novel, qualitative enzyme immunoassay based on fluorescence detection for determination of beta-lactam antibiotics in raw, commingled milk (Fluorophos BetaScreen E. U. test) was evaluated. A dose-response profile for penicillin G was constructed by analysis of spiked milk samples. The limit of detection, defined as the concentration of penicillin G that resulted in 95% of the samples being evaluated as positive, was 1.8 micrograms/kg. The repeatability of the assay was very high both within and between the three participating milk quality testing laboratories. In total 5,061 randomly selected tanker milk samples were analyzed with the BetaScreen test and compared with the Delvotest SP. The agreement between the two tests was 99.7%. Probably due to a higher sensitivity to penicillin G, the BetaScreen test detected almost twice as many suspect positive tanker milk samples (0.45%) as the Delvotest SP (0.26%).

Animals↗
PubMed1997

Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men.

OBJECTIVE: To examine the effect of grapefruit juice on the metabolism of felodipine following intravenous and oral administration. METHODS: The study had a randomised, four-way, crossover design in 12 healthy males. Single doses of felodipine were given as an intravenous infusion for 1 h (1.5 mg) or as an oral extended release (ER) tablet (10 mg). Grapefruit juice (150 ml) or water was ingested 15 min prior to drug intake. RESULTS: Intake of grapefruit juice did not significantly alter the intravenous pharmacokinetics of felodipine compared to control treatment, whereas after oral drug administration it did lead to an increase in the mean AUC and Cmax by 72% and 173%, respectively, and the mean absolute bioavailability was increased by 112%. The fraction of the oral felodipine dose reaching the portal system was increased from 45% to 80% when intake of drug was preceded by grapefruit juice ingestion. The pharmacokinetics of the primary metabolite, dehydrofelodipine, was affected by the intake of juice, resulting in a 46% increase in Cmax. Juice intake immediately before oral felodipine resulted in more pronounced haemodynamic effects of the drug as measured by diastolic blood pressure and heart rate. However, the haemodynamic effects of the intravenous administration were not altered by juice intake. Vascular-related adverse events were reported more frequently when oral drug administration was preceded by juice intake compared with control treatment. Taking grapefruit juice immediately prior to intravenous felodipine administration did not cause any alteration in the adverse event pattern. CONCLUSION: The main acute effect of the grapefruit juice on the plasma concentrations of felodipine is mediated by inhibition of gut wall metabolism.

Administration, Oral↗
PubMed1995

Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects.

In this randomised, cross-over study, in nine healthy males given felodipine ER 10 mg PO 200 ml grapefruit juice was found to increase the plasma levels of felodipine even when the juice was taken 24 hours before the drug. Grapefruit juice drunk simultaneously with and 1, 4, 10 or 24 hours before the drug administration resulted in a 32-99% increase in mean Cmax values of felodipine, relative to concomitant water and felodipine intake. The effect on AUC was also significant when juice was taken up to 10 h before the drug. The effect of the interaction decreased with increasing time between juice and drug intake. All treatments produced a significant decrease in diastolic blood pressure and an increase in heart rate in comparison with morning basal values. The change in haemodynamic variables was approximately the same after all treatment combinations. Headache was reported more frequently after treatments including grapefruit juice.

Adult↗
PubMed1993

The acute haemodynamic and renal effects of oral felodipine and ramipril in healthy subjects.

The aim of the present investigation was to compare the acute haemodynamic and renal effects of the calcium antagonist felodipine with the ACE inhibitor ramipril and with placebo. Single oral doses of felodipine 5 and 20 mg, ramipril 2.5 and 10 mg, and placebo were given to ten healthy subjects in a double-blind cross-over study. Blood pressure, heart rate, forearm blood flow (FBF), forearm vascular resistance (FVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction (FF), diuresis, and sodium excretion were recorded for 4.75 h after administration. Felodipine 20 mg caused a significant fall in diastolic blood pressure, maximal 12% compared with placebo, while there were no significant effects of felodipine 5 mg or the two doses of ramipril. Heart rate increased significantly after both doses of felodipine, maximal 28% after the 20 mg dose. There was also a small but significant increase in heart rate of 12% after ramipril 2.5 mg. FVR fell significantly after both doses of felodipine, maximal 38% after the 20 mg dose. There were no significant changes in FVR after any of the ramipril doses. Both doses of felodipine and both doses of ramipril caused significant reductions in RVR. Maximal reduction, 33%, was found after felodipine 20 mg. There were no significant changes in GFR or FF with either drug. Felodipine caused a significant increase in natriuresis, maximal 129% while ramipril did not.

Administration, Oral↗
PubMed1992

Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance.

The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1, and in the AUC from 23 to 65 nmol.h.l-1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs. The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (-9%) than did water (0%).

Adult↗
PubMed1989

Pharmacokinetics of felodipine in patients with impaired renal function.

1. The pharmacokinetics of felodipine and its effects on blood pressure and heart rate were studied in eight male patients aged between 28 and 57 years with a glomerular filtration rate, GFR, between 8 and 68 ml min-1, following single i.v. and oral administration. 2. Clearance, Cmax, AUC, Vss and V, of felodipine were unaffected by the renal disease. The metabolite excretion (14C-labelled) was slower than in healthy subjects. Initial renal clearance of these metabolites correlated with individual GFR values. The total amount of the dose excreted in the urine was also decreased.

Administration, Oral↗
PubMed1985

Felodipine kinetics in healthy men.

In a randomized, crossover study, the absorption, distribution, and elimination of intravenous and oral felodipine were investigated in eight healthy men 22 to 31 years old. Felodipine was given as a 2.5 mg iv infusion over 30 minutes and as a 27.5 mg oral solution. Both doses were labeled with 25 microCi 14C-felodipine. Given as an oral solution, felodipine is rapidly (mean time to peak concentration 64 minutes; range 30 to 90 minutes) and completely absorbed. Presystemic elimination reduced the availability to 16% (range 10% to 25%). Felodipine kinetics can be described by a multicompartmental model with three distinct phases. The t1/2 for the initial phase was 6.4 minutes (range 1.7 to 10.4 minutes) and felodipine was distributed to a volume of 0.6 L/kg (range 0.4 to 0.9 L/kg), which approximately corresponds to the total body water. The second distribution phase reached pseudoequilibrium with a t1/2 of 1.6 hours (range 1.3 to 2.2 hours). The volume of distribution at the end of this phase was 9.7 L/kg (range 6.0 to 18.2 L/kg). The terminal phase had t1/2 of 10.2 hours (range 6.7 to 20.7 hours). The contribution of the three phases to the AUC was 15%, 40%, and 45% in the order of increased t1/2. Total body clearance of felodipine was 1.2 L/min (range 0.9 to 1.6 L/min). Within 72 hours after drug dosing, 62% to 81% of the felodipine doses were excreted in the urine and feces as metabolites. The rate of excretion by the kidneys had a biphasic pattern, with t1/2 values of 4 and 18 hours. Approximately 10% of the doses was excreted in the feces.

Administration, Oral↗
PubMed1984

Pharmacokinetics of lidocaine in healthy individuals pretreated with multiple doses of metoprolol.

The effect of pretreatment with multiple doses of 100 mg of metoprolol on the pharmacokinetics of lidocaine has been studied in six young healthy subjects. The lidocaine dose was 100 mg and the infusion time 12 minutes. Metoprolol had no effect on the levels or the time course of lidocaine in the plasma. The disposition characteristics of the antiarrhythmic agent were not significantly altered by metoprolol in these individuals. These results cannot be extrapolated to prolonged infusion of lidocaine in patients with myocardial infarction.

Adult↗
PubMed1983

Haemodynamic effects of a new vasodilator drug, felodipine, in healthy subjects.

The haemodynamic effects of a new vasodilating drug, felodipine, were studied in eight, healthy, male subjects, aged 22-31 years. The drug was given as an oral solution in the dose of 0.15 mg/kg. Thirty-five minutes later further dose of 0.15 mg/kg was administered. Felodipine induced a pronounced decrease in diastolic blood pressure (maximal effect 15 +/- 4 mm Hg) and in the systemic vascular resistance. Cardiac output increased (maximum by 4.2 +/- 0.31/min), due to an increase both in the stroke volume and the heart rate. The maximal increase in the stroke volume (measured from echo cardiograms) and the heart rate were 33 +/- 5 ml and 23 +/- 3 beats/min, respectively. Felodipine caused a significant decrease in the pre-ejection period (23 +/- 3 ms) and an increase in the left ventricular ejection time (29 +/- 3 ms). The quotient PEP/LVET fell from 0.36 +/- 0.01 to 0.28 +/- 0.01. Significant activity of felodipine could be recorded at a plasma level of about 15 nmol/l. When the maximal haemodynamic effects were recorded the plasma level was about 40 nmol/l. After a cumulative dose of 0.30 mg/kg, there was a twofold variation in the maximal plasma level (from 31 to 61 nmol/l). The results of the present investigation are in agreement with previous haemodynamic studies in animals. It would appear that felodipine is a potent arteriolar vasodilator and it might well be of considerable value in the management of patients with hypertension or congestive cardiac failure.

Adult↗
PubMed1983

The systemic and coronary haemodynamic effects of felodipine in patients with coronary heart disease.

The cardiovascular effects of felodipine, a new arteriolar vasodilator, were studied in 22 patients with coronary heart disease. There were significant falls in blood pressure and systemic vascular resistance of 16 and 38% respectively (P = 0.001), thus affecting after-load. Cardiac index and stroke index increased by 35 and 12% respectively. There was reflex tachycardia--from 75 +/- 3 to 85 +/- 3 b.p.m. (P = 0.005). Coronary sinus blood flow increased from 134 +/- 9 to 191 +/- 17 ml/min (P less than 0.005) and myocardial arterio-venous oxygen difference narrowed from 12.1 +/- 0.5 to 9.0 +/- 0.4 vols% (P less than 0.001) indicating less oxygen usage. With the heart rate held constant by atrial pacing, cardiac index and stroke index increased by 30 and 26% (P less than 0.001), whilst systolic blood pressure and systemic vascular resistance fell by 20 and 29% (P less than 0.001). This would suggest that the improved haemodynamics were largely secondary to after-load reduction.

Adult↗
PubMed1982

Pharmacodynamic effects of prenalterol in healthy subjects.

1. Prenalterol induces a dose-dependent effect on different variables reflecting myocardial contractility and heart rate. A clearcut effect can be demonstrated after an oral dose of 2.5 mg. The duration of the effect increases considerably when prenalterol is administered as a controlled release preparation partly due to an increased bioavailability. 2. Prenalterol induces a lipolytic effect manifested as a rise in free fatty acids and glycerol. Also a slight increase of plasma insulin is recorded while plasma potassium decreases somewhat. 3. When prenalterol is administered together with therapeutic doses of a selective or non-selective beta-adrenoceptor blocker it induces the same haemodynamic effects as before the beta-blocker but the dose has to be increased ten-fold. These results suggest that prenalterol might be a useful drug to counteract unwanted haemodynamic effects of a beta-blocker. 4. In animal studies it has been shown that prenalterol has affinity for both beta 1- and beta 2-adrenoceptors. However, it has a stimulating effect mainly on beta 1-adrenoceptors. Therefore, theoretically it might act as a beta 2-adrenoceptor antagonist. Preliminary results from studies in patients with chronic asthma indicate that prenalterol only has an insignificant beta 2-blocking effect when the drug is administered in doses which induce a significant beta 1-adrenoceptor stimulating effect.

Administration, Oral↗
PubMed1981

Pharmacokinetic studies in man of the selective beta 1-adrenoceptor agonist, prenalterol.

The pharmacokinetics of prenalterol, a selective beta 1-adrenoceptor agonist, has been studied in healthy subjects, by following the plasma concentration and urinary excretion of the unchanged compound and its total radioactive metabolites after oral and intravenous administration. Each of six healthy subjects received a single i.v. dose (2.5 mg) and three oral doses (2.5, 5.0 and 10 mg) of prenalterol. The oral dose was administered as a solution. Three of the subjects received the intravenous and oral doses of 2.5 mg as tritiated drug. Prenalterol was rapidly and completely absorbed after oral administration. The peak plasma concentration was attained after about 0.5 h. About 25% of prenalterol reached the systemic circulation. Prenalterol was extensively distributed to extravascular tissues with a half-life of the distribution phase close to 7 min. About 90% of the dose was excreted in urine within 24 h irrespective of the route of administration, indicating complete absorption of the drug. On average 60% of the i.v. and 13% of the oral doses were excreted as unchanged drug. The elimination half-life of the compound was 1.8 h, and the decline in the plasma concentration of the metabolites indicated a slower elimination rate than for the unchanged drug. Dose-dependent kinetics were not observed after the oral doses examined.

Administration, Oral↗
PubMed1981

A dose-response study on metoprolol in angina pectoris.

The effects of 50, 100 and 200 mg oral single doses of metoprolol were compared in 23 patients with stable angina pectoris, previously treated with 50 mg metoprolol t.i.d. Treatment was stopped for one week and during this week patients received 50, 100 or 200 mg metoprolol in a randomized order as a single dose, with 48 hours between doses. Exercise tests were performed on a bicycle ergometer 1.5 h after tablet intake. At rest, systolic blood pressure was the same on all three doses while the heart rate was lower after 200 mg than after 50 mg of metoprolol (57 and 54 beats/min, respectively; p less than 0.01). During exercise, mean heart rate at the highest comparable work load was 101, 95 and 89 beats/min on 50, 100 and 200 mg metoprolol, respectively (p less than 0.001 for differences between doses). Corresponding values for systolic blood pressure were 177, 177 and 168 mm Hg. Total work performed and time until onset of pain were significantly higher on 200 mg than on 100 mg (p less than 0.05) or 50 mg (p less than 0.05). In a follow-up study which comprised one month's treatment with 100 mg b.d. and one month on 200 mg b.d., the majority of patients preferred treatment with metoprolol 100 mg b.d.

Aged↗