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Biomedical subjects

I W Reimann

Publications and source records attributed to I W Reimann.

28 records · Page 2Linked to original sources
PubMed1983

Indomethacin but not aspirin increases plasma lithium ion levels.

The pharmacokinetic drug interactions between lithium sulfate and the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin and aspirin were studied in ten normal female volunteers restricted to 150-mEq/day of sodium. Indomethacin decreased renal lithium ion elimination by 23% and caused a 40% increase in steady state plasma lithium ion levels. In contrast, aspirin had no effect on plasma lithium ion levels and increased renal lithium ion elimination by only 6%. Renal prostaglandin E2 excretion was suppressed by 50% to 60% of control levels by indomethacin and by 65% to 70% by aspirin. A clinically important drug interaction with the risk of lithium intoxication can occur between lithium salts and indomethacin. However, aspirin did not affect steady state plasma levels of lithium ion and thus may be preferable for antirheumatic treatment of patients undergoing long-term therapy with lithium salts. Frequent monitoring of plasma lithium ion levels is absolutely necessary in patients receiving both lithium salts and NSAIDs.

Adult↗
PubMed1983

Pharmacokinetics of ketanserin in man.

Kinetic data for the new antihypertensive agent ketanserin were determined in six healthy subjects after single oral (40 mg) or intravenous (0.15 mg/kg) doses. Plasma protein binding was 94.0 +/- 1.8% (mean +/- SD). Cumulative urinary excretion of unchanged drug was less than 4% within 48 h following the single dose. The maximal plasma level (Cmax) of 193 +/- 98.2 micrograms/l occurred within 0.5 to 4.0 h after oral intake. The ketanserin plasma level declined biexponentially after oral administration, and triexponentially over the 36 h following intravenous injection. The terminal elimination half-life (term. t 1/2) averaged 12.4 +/- 2.9 h and 12.8 +/- 4.8 h following oral and intravenous application, respectively. Total plasma clearance was 410 +/- 62.0 (i.v.) and 829 +/- 228 ml/min (p.o.) and the intravenous blood clearance averaged 602 +/- 91 ml/min, which indicates partly flow dependent hepatic elimination. A substantial first-pass effect led to a bioavailability of about 50% (range: 27-69%). Hepatic clearance of ketanserin followed the non-restrictive pattern. No change in blood pressure or heart rate was observed following ketanserin administration to normal volunteers.

Administration, Oral↗
PubMed1982

Effects of cimetidine and ranitidine on steady-state propranolol kinetics and dynamics.

The influence of cimetidine (1000 mg daily, one day oral pretreatment) and ranitidine (300 mg daily by mouth, 1 and 6 days pretreatment) on steady-state propranolol (160 mg sustained-release capsule, once daily) plasma levels (Psss) and dynamic beta-blocker effects was assessed by bicycle ergometer exercise and isoproterenol sensitivity test in five normal subjects. During the 3 hr of the dynamic tests Psss were elevated from 25% to 67% by cimetidine, whereas Pss was unchanged by ranitidine. The estimated hepatic blood flow (EHBF) as calculated from indocyanine green (ICG) plasma clearance was only slightly reduced by 15 +/- 23% (mean +/- SD, n = 4) after one oral dose of 150 mg ranitidine and showed substantial intersubject variability. Dynamic parameters, like propranolol-induced heart rate and blood pressure changes under physical exercise or during the isoproterenol sensitivity test, were not influenced by ranitidine or cimetidine. Since our study was performed on normal subjects with relatively low propranolol doses these results do not rule out the risk of severe reinforcement of beta-adrenergic receptor blocking effects if propranolol and cimetidine are taken together by patients.

Adult↗
PubMed1981

Effects of diclofenac on lithium kinetics.

The influence of the prostaglandin (PG) synthesis-inhibiting, nonsteroidal anti-inflammatory drug (NSAID) diclofenac on lithium kinetics was studied in five normal women on a 150-mEq sodium diet. Diclofenac decreased lithium renal clearance by 23% (P - 0.002) and increased lithium plasma levels by 26% (P - 0.001). Renal PG synthesis was suppressed by 53% of control values. These data show a clinically important drug interaction, possibly on the basis of a PG-dependent mechanism, with the risk of lithium intoxication for patients treated with lithium salts and NSAIDs.

Adult↗
PubMed1981

Are prostaglandins involved in the antihypertensive effect of dihydralazine?

1. Two female and two male patients with essential hypertension were given dihydralazine plus saline or dihydralazine plus diclofenac intravenously on two separate occasions. The dihydralazine dose (range: 16.2--32.4 mg/2 h) was chosen individually to reduce systolic blood pressure by 20 mmHg from the control value before the investigation; the intravenous diclofenac dose was 75 mg/20 ml of saline for all patients. 2. Dihydralazine decreased diastolic blood pressure more than systolic blood pressure and increased heart rate; diclofenac reduced both of these effects. 3. Dihydralazine increased urinary volume and sodium clearance; both these effects were antagonized by concomitant treatment with diclofenac. 4. Whereas dihydralazine did not influence creatinine clearance appreciably, concomitant administration of diclofenac reduced creatinine clearance. 5. Urinary prostaglandin E2 was reduced by diclofenac. 6. We suggest that dihydralazine-mediated vasodilation is reduced by cyclo-oxygenase inhibition.

Adult↗
PubMed1981

Cimetidine increases steady state plasma levels of propranolol.

1 The influence of cimetidine (1000 mg daily) on propranolol steady state plasma levels has been studied in seven normal volunteers. Cimetidine was used as a 200 mg normal release tablet whereas propranolol was given as a 160 mg slow release formulation once daily. 2 After 1 day of cimetidine treatment (day 9 of the study) the mean (Css) and minimal (Css min) propranolol steady state plasma levels increased significantly from 24.1 +/- 14.9 ng/ml (mean +/- s.d.) to 39.2 +/- 27.7 ng/ml (P = 0.01) and from 14.8 +/- 9.3 ng/ml to 27.1 +/- 21.2 ng/ml (P = 0.03), respectively. The apparent oral clearance (Clo) was reduced from 6.7 +/- 4.3 l/min to 4.6 +/- 3.11/min (P = 0.006). 3 A prolongation of cimetidine administration to 5 days (day 13 of the study) intensified this effect significantly (P = 0.02): Css of propranolol was elevated from 23.2 +/- 14.4 ng/ml to 44.9 +/- 26.7 ng/ml (P = 0.003); Css min was increased from 14.1 +/- 10.2 ng/ml to 28.4 +/- 17.9 ng/ml (P = 0.02) while Clo decreased from 6.9 +/- 4.1 1/min to 3.3 +/- 1.61/min (P = 0.006). 4 We conclude that the drug interaction between propranolol and cimetidine leads to significant elevations of propranolol steady state plasma concentrations which may cause a clinically relevant enhancement of the effect of a given dosage. This requires careful observation of patients under concomitant treatment with propranolol and cimetidine.

Adult↗
PubMed1981

[Risks of simultaneous tocolytic treatment with beta adrenergic and PG inhibiting agents].

Betaadrenergics are the most important agents in the treatment of premature labour. Often they are used in combination with steroids which promote fetal lung maturation and prevent respiratory distress syndrome in preterm infants. Because PG synthesis inhibitors also reduce uterine contractions they have been used as tocolytics whenever beta adrenergics alone fail. Several cases of pulmonary edema in otherwise healthy pregnant women have been reported following a combined tocolytic treatment with betaadrenergic drugs and PG synthesis inhibitors. The inhibited synthesis and function of renal PGs may be a very important factor contributing to those fatal events. Both, the ADH stimulating effect of beta adrenergics and the inhibition of the negative feed back mechanism of PGs on ADH action by blockade of PG synthesis potentiates renal water retention, thereby increasing the risk of water intoxication. Concerning the effects of maternal tocolytic treatment on the fetus or newborn, there is good evidence that PG inhibitors like aspirin or indomethacin can lead to closure of the ductus Botalli prior to birth and persistent pulmonary hypertension of the newborn. Severe cardiopulmonary adaption disturbances may be the consequence. Routine clinical use of PG synthesis inhibitors in combination with adrenergic stimulants cannot be recommended on the basis of available information.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Influence of prostaglandin inhibition on dihydralazine induced acute effects in patients with essential hypertension.

In order to determine whether vasodilator prostaglandins (PG) contribute to the acute vascular and endocrine responses to intravenously administered dihydralazine, we examined its effects on systolic and diastolic blood pressure (BP), heart rate (HR), plasma renin activity (PRA) and the plasma catecholamines (CA) noradrenaline (NA), adrenaline (A) and dopamine (DA) as well as on sodium, potassium and creatinine clearance (CNa, CK and CCr respectively), urinary flow rate, urinary catecholamines (NA, A, DA) and iPGE2 and i6-keto-PGF1 alpha excretion rate in six patients (three females, three males) with essential hypertension before and after PG synthesis inhibition by the nonsteroidal, anti-inflammatory agent diclofenac. Diclofenac, which reduced urinary iPGE2 and i6-keto-PGF1 alpha excretion by 62% (P = 0.026) and 45% (P = 0.037), respectively, antagonized dihydralazine induced diastolic BP reduction (P = 0.0009), HR increase (P = 0.01), noradrenaline and adrenaline increase in plasma (P = 0.02 and P = 0.05, respectively), increase in urine flow rate (P = 0.03), sodium clearance (P = 0.01) and tended to reduce PRA. We conclude that dihydralazine-mediated changes can be reduced by cyclo-oxygenase inhibition, most likely on the basis of a reduction of its effect on peripheral resistance, thereby leading to less reflex activation of the sympathetic nervous and renin-angiotensin systems.

Adult↗
PubMedDate not supplied

Chronopharmacokinetic study with prolonged infusion of midazolam.

Physiological and temporal variation in the disposition of midazolam has been reported. In order to delineate the underlying mechanisms of these alterations, we infused in 5 healthy male volunteers for 26 hours midazolam at a rate of 0.025 mg/kg/h preceded by a bolus of 0.05 mg/kg. Thus, steady-state conditions were rapidly achieved. Plasma levels of midazolam were monitored on a 2-hourly basis during this period. In addition, the pharmacodynamic response to the new sedative/hypnotic benzodiazepine was characterised by a pencil tracking test, sedation index formed from visual analogue scales, and choice reaction time. In all subjects, small (4 to 16%) but clinically irrelevant fluctuations of steady-state plasma concentrations around 45 ng/ml were observed. During the night-time (11pm to 7am) plasma concentrations were slightly (p = 0.074) higher than during the daytime. Total plasma clearance varied from 563 to 823 ml/min. Plasma protein binding of midazolam was time independent. Since in only 1 of 5 subjects was a circadian rhythm observed, fluctuations in plasma midazolam concentrations under controlled and constant conditions are probably not of clinical significance.

Adult↗