Lars Olof Boréus

Autonomic receptor function in the lower urinary tract of man and cat.

Autonomic receptor function was studied in vitro in smooth muscle strips from the lower urinary tract of children and cats. In strips from the dome of the bladder, cholinergic and β-adrenergic, but no α-adrenergic receptor function was demonstrated. In the bladder base as well as in the proximal urethra cholinergic and both α- and β-adrenergic receptors were found. This suggests that the sympathetic nervous system can subserve relaxation in the dome of the bladder and both contraction and relaxation in the bladder base as well as in the proximal urethra.

Fluoride bioavailability after intravenous and oral administration: importance of renal clearance and urine flow.

Fluoride (3 mg) was administered as a continous intravenous infusion during 30 min to 6 healthy subjects. Plasma concentrations and urinary excretion of fluoride in these experiments were compared with those obtained following oral administration of 2.82 mg, 4.50 mg, 5.64 mg, and 9.40 mg in the form of tablets and capsules. There were large day‐to‐day variations in the renal clearance of fluoride. This was shown to be due to differences in the urinary flow, an increase in flow causing an increase in renal clearance. The mean value of renal clearance from all experiments was 66.2 ± 27.8 (SD; n = 16) mllmin. The extrarenal clearance, suggested to represent mainly the clearance to the bone pool, showed less interindividual variation: mean 110.3 ± 32.3 (SD; n = 6) ml/min; the fraction remaining in the bone pool was highly consistent: 0.579 ± 0.049 (SD; n = 6). When apparent bioavailability was calculated from plasma and from urinary data, there was a great intra‐ and intersubject variation, as well as poor agreement between the two methods of calculations. This was found to be due to the day‐to‐day variation in renal clearance, which, in turn, varied with urinary flow. By use of equations that corrected for these variations, it was found that the bioavailability of sodium fluoride tablets is approximately 100%.

Pentazocine binding to blood cells and plasma proteins

The binding of pentazocine to human whole blood, plasma, and blood cells was investigated in 20 normal subjects and 22 patients by means of equilibrium dialysis. Plasma protein binding was 56% to 66% in the control sub;ects and 48% to 75% in the patients. In control sub;ects, 48% of the total amount of pentazocine in whole blood is present in blood cells and 33% is bound to plasma proteins. The remaining 19% is in the plasma water. Whole blood concentrations of pentazocine may be expected to be about the same as the plasma concentrations in sub;ects with normal hematocrit.

Pharmacokinetic Interactions Between Lamotrigine and Other Antiepileptic Drugs in Children with Intractable Epilepsy

Summary: Purpose: We wished to determine the oral pharmacokinetics of lamotrigine LTG and to assess possible interactions with other AEDs in an unselected population of children. Concentration data in plasma and in CSF for lamotrigine as well as for the other AEDs are presented.

Bioavailability and first‐pass metabolism of oral pentazocine in man

The bioavailability of oral pentazocine was studied in 5 healthy volunteers. Plasma concentrations were determined from 30 min up to 6 hr following oral administration (two 50‐mg tablets) and, at other occasions, after intravenous injection of 30 mg pentazocine. The average bioavailability was found to be 18.4 ± 7.8% (SD, n = 5). It is shown that this low bioavailability depend almost entirely on the first‐pass metabolism of pentazocine following oral administration by application of intravenous clearance concepts. The average beta‐phase half‐life was about the same following intravenous administration, 203 ± 71 (SD, n = 5) min as following oral administration, 177 ± 34 (SD, n = 5) min, with a total volume of distribution of 5.56 ± 1.63 (SD, n = 5) Llkg. It is suggested that the variations in bioavailability of orally administered pentazocine have the potential to contribute to variations in pharmacologic effects in patients.

Pharmacokinetics of ampicillin and its prodrugs bacampicillin and pivampicillin in man

Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491 mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 ± 0.045 (sd) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 ± 11%) and pivampicillin (92± 18%) was significantly greater than that of ampicillin (62 ± 17%); however, the difference between the esters was not statistically significant. The absorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The absorption rate was highest for bacampicillin (0.89 ± 0.39% of dose absorbed per minute), followed by pivampicillin (0.64 ± 0.19) and ampicillin (0.58 ± 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 ± 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.

Chiral analysis of methadone in plasma by high-performance liquid chromatography.

A method for the chiral high-performance liquid chromatographic analysis of methadone in plasma has been developed. The method employed organic solvent extraction, enantiomeric separation on a Chiral AGP column, and ultraviolet absorption detection at 212 nm. The intra-day variation in the quantification of methadone enantiomers was less than 9% at the 100 ng/ml level, and the values obtained correlated well with those from a gas chromatographic-mass spectrometric method. Results from patients indicate inter- and intra-individual differences in the ratio between l- and d-methadone in plasma during therapy with racemic methadone. In one patient, a higher level of d-methadone in plasma was caused by both faster elimination and lower bioavailability of l-methadone.

Immunological screening of benzodiazepines in urine : improved detection of oxazepam intake

Immunological screening analysis of benzodiazepines in urine using the EMIT (enzyme multipled immuno-technique) and FPIA (fluorescence polarization immunoassay) techniques does not reliably detect the intake of therapeutic doses of oxazepam. In 23 patient urine samples, in which the presence of oxazepam could be verified chromatographically, only about 50% were detected as positive in the immunoassay systems. However, when the screening procedure was modified to include a simple step of hydrolysis of urine using the enzyme beta-glucuronidase to liberate conjugated oxazepam, improved detection of oxazepam intake was achieved. With EMIT 95% and with FPIA 100% of the samples were detected as positive. Since oxazepam arises in vivo also as a metabolite of other common benzodiazepines, the modification will most likely contribute to the generally improved detection of benzodiazepines.

Influence of Atropine and Isoprenaline on Detrusor Hyperactivity in Children with Neurogenic Bladder

Bladder hyperactivity defined as unconscious, involuntary detrusor contractions giving rise to intravesical pressure increase of at least 15 cm H2O and of minimum 15 sec duration, has been examined in 9 children with myelodysplasia and incontinence. The effect of atropine and isoprenaline on the hyperactivity pattern was evaluated. Atropine had a dose-related inhibiting influence on both frequency and amplitude of detrusor contractions whereas isoprenaline was without these favourable effects.

The Inhibitory Effect of Coli-Endotoxin on Alpha-Adrenergic Receptor Functions in the Lower Urinary Tract: An In vitro Study in Cats

The effects of endotoxin from E. coli 06 on alpha-adrenergic receptor functions have been investigated in muscle strips from the outlet region of the feline bladder. The endotoxin from this strain, known to cause urinary tract infections, inhibited the alpha-adrenergic contractions induced by phenylephrine and noradrenaline. This inhibition was dose-dependent, correlated to time of exposure, and reversible. Alpha-adrenergic receptor function in muscle strips from cat aorta was also inhibited, but not cholinergic stimulation of muscle segments from the bladder.