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Biomedical subjects

B Norlander

Publications and source records attributed to B Norlander.

At least 37 records · Page 2Linked to original sources
PubMed1989

Tissue distribution of glyceryl trinitrate and the effect on cGMP levels in rat.

In order to study distribution in tissue, rats were treated subcutaneously with glyceryl trinitrate, GTN, (50 mg/kg). The concentrations of GTN were measured in plasma, brain, heart, adipose tissue and aortic tissue at different sampling times by a gas chromatographic method with electron-capture detection. The peak GTN-concentration was reached after 2 hours in all tissues examined. The highest concentration of GTN was found in adipose tissue, where the level was approximately forty times higher than in plasma. The concentration of GTN in brain, heart and aortic tissue was about 2-3 times as high as in plasma. The cGMP level was measured in heart and brain. An increase of the cGMP level was found in brain 2 hours after GTN administration. No cGMP increase was found in heart tissue. The results indicate a substantial distribution of GTN to tissue, and an increase of cGMP in brain. The distribution of the substance in the tissues as shown, might have both pharmacokinetic and pharmacodynamic implications.

Adipose Tissue↗
PubMed1988

Pharmacokinetics of chloral hydrate poisoning treated with hemodialysis and hemoperfusion.

In a severe case of chloral hydrate intoxication treated with combined hemodialysis and hemoperfusion the pharmacokinetics of the metabolites trichloroethanol (TCE), trichloroethanol glucuronide (TCE-Glu) and trichloroacetic acid (TCA) were studied. Indications of delayed absorption and some slowing of metabolism were found. At a blood flow rate of 200 ml/min clearances by hemodialysis and hemoperfusion, respectively, in ml/min were estimated to be 188 and 156 for TCE, 184 and 181 for TCE-Glu, 142 and 91 for TCA. Clearance by hemoperfusion declined with time. The half-lives of TCE and TCA were 3.2 and 4.3 hours during combined hemodialysis and hemoperfusion. After termination of treatment the half-life of TCE was 12.8 hours, whereas TCA was metabolized so slowly, that no reliable calculation could be performed. We conclude that hemodialysis and hemoperfusion are equally and highly efficient in the treatment of chloral hydrate poisoning, but hemoperfusion may increase the risk of gastric bleeding more than hemodialysis. Hemodialysis may therefore be preferable and should be tried in spite of low blood pressure.

Adult↗
PubMed1988

Variable bioavailability of papaverine.

The plasma concentration curves of papaverine have been studied in nine healthy males and seven patients after administration of single intravenous (80 mg) and oral (80 mg) doses. The bioavailability of the drug was highly variable with a mean of 28% (range 5-99%) but reproducible within the same individual (4 of the volunteers) after a repeated (80 mg) oral dose. The calculated half-life after intravenous administration ranged between 1.2-6.6 hours (mean 3.0). The mean apparent volume of distribution was 3.1 l/kg and the mean total plasma clearance was 836 ml/min. It is concluded that papaverine shows an unacceptable inter-individual variation in the bioavailability after oral administration of 80 mg tablets.

Administration, Oral↗
PubMed1988

Attomole sensitive radioimmunoassay for cyclic GMP.

The sensitivity of the radioimmunoassay for cyclic GMP has been improved to readily detect attomole (200-300) amounts of the nucleotide in tissue extracts. The improved sensitivity has been achieved by using a high specific radioactivity [125I] cyclic GMP 2'O-succinyl tyrosine methyl ester (2200 Ci/mmole) as labeled antigen in conjunction with acetylation of the cyclic GMP in the samples as well as by using a selected cyclic GMP antibody. The high specific [125I] cyclic GMP 2'O-succinyl tyrosine methyl ester was prepared radiochemically pure by radioiodination of cyclic GMP 2'O-succinyl tyrosine methyl ester and purification using HPLC. The new attomole sensitive cyclic GMP radioimmunoassay is simple to perform and fast and has been applied with success to determine attomole quantities of cyclic GMP in cultured smooth muscle cells and AG 1523 fibroblasts.

Animals↗
PubMed1987

Retention and subsequent liberation of glyceryl trinitrate in organ baths influences the relaxation of bovine mesenteric arteries contracted by various agents.

The present study compares the relaxant effect of glyceryl trinitrate (GTN) on isolated bovine mesenteric artery in commonly used organ baths made of glass and in disposable vials made of polyethylene, a material known to be inert to GTN. It is shown that the EC50-value for the GTN-induced relaxation is about 1000-fold lower when polyethylene vials are used. The study also shows that the reason for this is that the materials previously used in the experimental equipment retain and subsequently liberate GTN at re-use. In organ baths of glass with holders of acrylics, GTN concentrations of about 20 nM were found during equilibration, i.e. before start of the experiment. The vessel specimens become partly tolerant during equilibration in such organ baths and thus the vessels are less sensitive to GTN. The findings may explain the discrepancy between previous in vitro and in vivo studies. Low concentrations known to be effective in vivo have not been demonstrated to have a relaxant effect in earlier in vitro studies.

Animals↗
PubMed1986

Sensitive assay of methadone in plasma by using capillary gas chromatography with photoionization detection.

A new gas chromatographic assay for methadone, utilizing a fused-silica capillary column, is presented. Extreme sensitivity was reached, compared to nitrogen-phosphorus and mass spectrometry detection, by employing a photoionization detector. Plasma concentrations of methadone as low as 1 ng/ml can easily be detected and, by further optimization, 0.1 ng/ml was reached. The minimum detectable amount of methadone reaching the detector was 70 fg. The results indicate that the photoionization detector has potential as a tool in drug monitoring.

Chromatography, Gas↗
PubMed1984

Repeated pentagastrin-stimulated gastric acid secretory tests carried out in the evaluation of the pharmacodynamics of a new histamine H2-receptor antagonist, SK&F 93479.

Single doses of 10 mg or 20 mg intravenously or 25 mg or 40 mg orally of a new histamine H2-receptor antagonist, SK&F 93479, have been administered to 31 patients with peptic ulcer disease. BAO and MAO were measured before and repeated during a 26-h period after drug administration. In a separate group of 17 patients the mean coefficients of variation of BAO and MAO measured in this manner were 53% and 20%, respectively. If this variation in the placebo group is taken into account, BAO was significantly inhibited at all dose levels during the 3rd h after dosing, and a significant effect was still seen during the 25th h after 40 mg orally with a mean reduction of 77%. Mean inhibitions of MAO during the 4th h after dosing of SK&F 93479 were significant at all dose levels, and a significant effect could still be seen during the 26th h for the two oral doses. The mean inhibitions of MAO measured during the 4th and 10th h after dosing were after 10 mg intravenously 44% and 11%, after 20 mg intravenously 59% and 11%, after 25 mg orally 57% and 21%, and after 40 mg orally 75% and 46%. The percentage inhibition of MAO during the 10th h correlated with plasma concentrations (r = 0.64, p less than 0.01). SK&F 93479 is a potent inhibitor of acid secretion with a long duration of action.

Administration, Oral↗
PubMed1983

Prizidilol, a combined vasodilatory and beta-adrenoceptor blocking drug, in primary hypertension. A long-term efficacy, tolerance and pharmacokinetic study.

After an initial placebo period of four weeks 24 patients with primary hypertension were treated with prizidilol, a hydrazinopyridazine derivative with combined vasodilator and non-selective beta-adrenoceptor blocking actions, for a dose titration period of 14 weeks. Prizidilol 200 to 800 mg was given once daily to achieve a target supine diastolic blood pressure (BP) less than 90 mmHg. Supine and standing BP recorded 24-27 h after drug intake decreased from 172 +/- 17/106 +/- 6 mmHg (mean +/- SD) and 167 +/- 18/111 +/- 8 mmHg, respectively, after placebo to 159 +/- 16/99 +/- 8 and 154 +/- 18/101 +/- 9 mmHg after active treatment for six weeks (mean dose 447 mg), and to 154 +/- 16/97 +/- 7 and 148 +/- 14/97 +/- 7 mmHg after treatment for 14 weeks (mean dose 687 mg/day). A slight reduction in HR was seen after treatment for six weeks and in plasma renin activity and urinary methoxycatecholamine excretion after treatment for 14 weeks. A sustained decrease in BP was observed for 10 h after prizidilol 800 mg (n = 9), with a maximum antihypertensive effect (mean reduction in supine BP 33/18 mmHg) 2.5 h after dosing, which coincided with the mean peak plasma concentration. The plasma elimination half-life of the drug was 3.9 h (range 2.0-8.9 h). Changing to a twice daily regimen in 17 patients (mean daily dose 748 mg at six months) did not produce any further reduction in the BP (recorded 12-15 h after dosing) as compared to the once daily regimen at 14 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1983

Pharmacokinetics of oxmetidine, a new histamine H2-receptor antagonist, after single oral and intravenous doses.

The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53-91%). After intravenous administration, the mean plasma t 1/2 beta was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.

Administration, Oral↗
PubMed1983

Effect of cimetidine and oxmetidine on 24-h gastric acid and pepsin in patients.

The 24-h intragastric pH, titrated hydrogen ion concentration, and pepsin concentration were studied in nine peptic ulcer patients during administration of placebo and of 800 mg cimetidine given as two or four equal doses. Cimetidine, 400 mg twice daily, was more effective in reducing acidity during morning (p less than 0.05) and overnight (p less than 0.01) than cimetidine, 200 mg four times daily, which, however, was the most effective regimen during the afternoon (p less than 0.05-0.01). During the 24-h period pH values equal to or above 5 were observed for less than 1 h with placebo treatment, for 1.8 h with cimetidine, 200 mg four times daily, and for 4.7 h with cimetidine, 400 mg twice daily. A new histamine H2-receptor antagonist, oxmetidine, was studied in six other patients, also during a 24-h period. Both 400 mg twice daily and 200 mg four times daily of oxmetidine were superior to placebo (p less than 0.05) in reducing intragastric acidity during the entire 24-h period.

Adult↗
PubMed1982

Pharmacokinetics of cimetidine and its sulphoxide metabolite during haemodialysis.

A single intravenous dose of cimetidine 200mg was administered to 6 patients with severe chronic renal failure one hour prior to haemodialysis. The plasma concentrations of cimetidine and its sulphoxide metabolite at the start of haemodialysis were 2.74 +/- 0.12 and 0.76 +/- 0.08 microgram/ml, and after dialysis for 4h 1.08 +/- 0.10 and 0.51 +/- 0.08 microgram/ml, respectively (mean +/- SE). The average haemodialysis clearance (ClHDa) of cimetidine during dialysis was 46-92 ml/min at a dialysate flow rate of 320 ml/min and blood flow rates in the 6 patients between 160-240 ml/min. The mean ClHDa of the sulphoxide metabolite was 44% higher than that of cimetidine, and ranged between 49-148 ml/min. During haemodialysis the mean plasma elimination half-life (t 1/2) of cimetidine was 3.24h (range 2.08-5.08) and of the sulphoxide metabolite 9.49h (range 4.70-14.39). There was a significant relationship between the elimination rate constant (beta) and ClHDa of the sulphoxide metabolite (p less than 0.01), but no such relationship was found between beta and ClHDa of cimetidine. The mean total amount of cimetidine eliminated during dialysis was 27.3mg (range 17.9-31.8), which was 9.0-15.9% of the given dose. Between 12.2-21.2mg (mean 15.3) of the sulphoxide metabolite was eliminated in the dialysate. Major adjustment of the dose of cimetidine on days of dialysis is not necessary.

Adult↗
PubMed1982

The pharmacokinetics of cimetidine and its sulphoxide metabolite in patients with normal and impaired renal function.

1 The pharmacokinetics of cimetidine and its sulphoxide metabolite was studied after a single intravenous dose of 200 mg cimetidine in nine patients with normal renal function and ten patients with severe renal failure on regular haemodialysis and during continuous oral cimetidine treatment in ten patients with normal renal function and 31 patients with different degrees of renal failure. 2 In normal renal function a mean of 47.3% of the single intravenous dose was excreted as unchanged drug and 12.8% as cimetidine sulphoxide. The mean plasma elimination half-life (T1/2) of cimetidine was 2.0 h and of cimetidine sulphoxide 1.7 h. 3 In severe renal failure a mean of 2.2% of the single intravenous dose was excreted as unchanged drug and 0.5% as cimetidine sulphoxide. The mean plasma T1/2 of cimetidine was 3.9 h. The plasma concentrations of the sulphoxide metabolite increased successively with time after dosing and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients g and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients g and no elimination phase was observed still 9 h after dose. The mean non-renal clearance of cimetidine was 210 ml/min and lower than in normal renal function, suggesting decreased metabolism of cimetidine in uraemia. 4 During continuous oral cimetidine treatment in patients with normal renal function and in patients with different degrees of renal failure given reduced doses of cimetidine the plasma concentrations of the sulphoxide metabolite were higher with decreasing renal function. The mean plasma T1/2 of cimetidine was 3.1 h in mild renal dysfunction (creatinine clearance 50-75 ml/min) and 4.5 h in severe renal failure (creatinine clearance 5-15 ml/min) and of cimetidine sulphoxide 5.3 and 14.4 h respectively. 5 Toxicity studies of cimetidine sulphoxide may be needed to assess if high plasma concentrations of the sulphoxide metabolite in severe renal failure are of clinical significance.

Administration, Oral↗
PubMed1982

Cimetidine, but not oxmetidine, penetrates into the cerebrospinal fluid after a single intravenous dose.

1 Thirty-six patients with various neurological diseases or symptoms received single intravenous doses of either cimetidine 400 mg (n = 19) or oxmetidine 200 mg (n = 17), 15 or 60 min before a diagnostic lumbar puncture. 2 In the 15 min CSF samples concentrations of cimetidine were detectable but not measurable in 5 and non-detectable in 3 patients. 3 In the 60 min CSF samples the concentrations of cimetidine were detectable in all 11 patients and were measurable in 8 of these patients with a mean +/- s.e. mean of 0.12 +/- 0.01 microgram/ml. These CSF concentrations were correlated to simultaneously measured plasma concentrations (P less than 0.01). The mean ratio CSF/plasma concentration was 0.03. 4 No detectable concentrations of oxmetidine were found either in the 15 min (n = 9) or in the 60 min (n = 8) liquor samples. 5 Cimetidine penetrates the blood-drain barrier slowly and not freely after a single dose. Our data suggest that the new histamine H2-receptor antagonist oxmetidine does not cross this barrier.

Adult↗
PubMed1981

Prizidilol, an antihypertensive with precapillary vasodilator and beta-adrenoceptor blocking actions, in primary hypertension.

Single oral doses of 1.5, 3.0, 4.5 and 6.0 mg/kg prizidilol HCl, an antihypertensive with vasodilator and beta-adrenoceptor blocking actions, were given to 12 patients with primary hypertension on separate days. Systolic and diastolic blood pressure (BP) decreased after 4.5 and 6.0 mg/kg and systolic BP also after 3.0 mg/kg. The antihypertensive effect was evident in 1 to 2 hr with maximum effect in 4 to 5 hr (supine systolic BP 20 and diastolic 13 mm Hg after 6.0 mg/kg); the effect was sustained for more than 8 hr. An initial slight reduction in heart rate (HR) after 1 to 2 hr was followed by a slight rise after 6 to 8 hr. There were higher plasma drug levels and greater antihypertensive effects after the 6.0-mg/kg dose in slow acetylators (n = 5) than in rapid acetylators (n = 7). Due to its hydrazine moiety, prizidilol, like hydralazine, seems to be a substrate for the polymorphic N-acetyltransferase enzyme system.

Adrenergic beta-Antagonists↗
PubMed1979

Oral absorption of cimetidine and its clearance in patients with renal failure.

The plasma concentration curve after a single oral dose of cimetidine 200 mg was followed in 27 patients with varying degrees of chronic renal failure (creatinine clearance 1--52 ml/min) and in 46 patients with normal serum creatinine. Compared to the latter patients, the plasma concentration was higher and the elimination rate was slower in all uraemic subjects, including a group with moderate renal impairment. The preliminary recommendations of dosage for patients with a creatinine clearance below 5 ml/min, and for patients on regular haemodialysis, is cimetidine 200 mg every 12 h, 5-15 ml/min 200 mg every 12 to 8 h, 15-30 ml/min 200 mg every 8 h and 30-52 ml/min 200 mg every 6 h.

Adult↗