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Biomedical subjects

B Lindström

Publications and source records attributed to B Lindström.

At least 91 records · Page 5Linked to original sources
PubMed1986

Whole-blood single-dose kinetics of chloroquine and desethylchloroquine in Africans.

The whole-blood kinetics of chloroquine and desethylchloroquine were studied in five healthy Ghanaian subjects. Chloroquine was rapidly absorbed, and peak concentrations were reached within 2 h. The drug disappeared from blood in a multiexponential manner, and the mean terminal half-life from day 7 to day 28 was 13 days. Desethylchloroquine concentrations were generally higher than those of chloroquine after 48 h. Renal clearance accounted for 65% of the apparent total clearance of chloroquine. The estimated mean total urinary recovery of the drug and its desethyl metabolite was 80% of the dose. Whole-blood concentrations of chloroquine offer some advantages compared with plasma concentrations, as this drug concentrates in the formed elements, and special precautions must be taken to obtain representative plasma concentrations.

Administration, Oral↗
PubMed1986

Enantioselective analysis of chloroquine and desethylchloroquine after oral administration of racemic chloroquine.

An enantioselective high-performance liquid chromatographic method for chloroquine and desethylchloroquine was developed using a chiral alpha 1-acid glycoprotein column. This method was used to determine concentrations of chloroquine and desethylchloroquine enantiomers in plasma and urine from volunteers given single oral doses of racemic chloroquine. The disposition of the enantiomers was different. The renal clearance of the chloroquine enantiomers was indicative of stereoselective renal secretion of the drug, and evidence for stereoselective metabolism also was found.

Adult↗
PubMed1986

Protein binding of chloroquine enantiomers and desethylchloroquine.

The protein binding of racemic chloroquine, its enantiomers and desethylchloroquine to plasma, purified human albumin, and alpha 1-acid glycoprotein (alpha 1-AGP) was determined by equilibrium dialysis. The binding was not concentration dependent. (+)-Chloroquine bound more to plasma (66.6 +/- 1.9%) and albumin (45.9 +/- 0.8%) than (-)-chloroquine (48.5 +/- 2.4% and 35.3 +/- 0.6%, respectively). These differences were statistically significant. (-)-Chloroquine bound more to alpha 1-AGP (47.5 +/- 0.7%) than (+)-chloroquine (34.5 +/- 0.5%). The binding of desethylchloroquine to alpha 1-AGP is higher than to albumin (38.9 +/- 0.9% and 21.1 +/- 0.4%, respectively.

Chloroquine↗
PubMed1986

Comparison of the pharmacokinetics of chloroquine after single intravenous and intramuscular administration in healthy Africans.

The pharmacokinetics of chloroquine were studied after intramuscular and intravenous administration of the drug to healthy African adults. Chloroquine was analysed in plasma using an h.p.l.c. method and pharmacokinetic parameters were derived from the concentration-time data using a non-linear computer programme. A two-compartment open model was assumed. Chloroquine was rapidly absorbed from an intramuscular site, producing a plasma concentration-time profile similar to that obtained after a 15 min i.v. infusion of a comparable dose. The pharmacokinetics of chloroquine after i.m. and i.v. administration were characterised by a long half-life and a very large volume of distribution. There was no significant difference between the values of each parameter obtained from the different routes. It is suggested that the high Cmax obtained after i.m. and i.v. administration of chloroquine might contribute to its toxicity when these routes are used in treatment.

Adult↗
PubMed1986

Pharmacokinetics of physostigmine after intravenous, intramuscular and subcutaneous administration in surgical patients.

The pharmacokinetics of physostigmine after intravenous, intramuscular or subcutaneous administration as well as its arousal effect after anaesthesia have been studied in surgical patients in the early postoperative period. After intravenous administration physostigmine had a very rapid plasma elimination with a plasma clearance ranging from 47 to 163 l/h with a mean +/- s.d. of 92.5 +/- 37.7 l/h. The volume of distribution was 46.5 +/- 19.2 l, while distribution and plasma elimination half-lives were 2.3 and 22 min, respectively. A fraction of the dose was probably hydrolyzed in blood since its blood elimination half-life in vitro was approximately 190 min. After both intramuscular and subcutaneous administration the systemic availability was almost complete, the plasma terminal half-lives only being somewhat longer than after intravenous administration. Plasma clearance, volume of distribution and elimination half-life of physostigmine were not correlated to age or body weight of the patients. The rapid plasma clearance of physostigmine resulted in a short duration of antisedative effect. After administration of 1 mg physostigmine salicylate i.v., drug-induced sedation was rapidly reversed with a duration of 30-60 min. The duration of action was similar after intramuscular injection but onset was delayed by 20-30 min. It was concluded that a plasma concentration of 3-5 ng/ml of physostigmine should be exceeded if an adequate analeptic effect is to be achieved, meaning that 2 mg of physostigmine had to be administered subcutaneously in order to achieve a satisfactory reversal of sedation. The short duration of action may hamper the use of physostigmine as an agent for reversal of drug-induced sedation and anticholinergic effects after surgery.

Adult↗
PubMed1986

Unscheduled DNA synthesis in lens epithelium after in vivo exposure to UV radiation in the 300 nm wavelength region.

A quantitative autoradiographic method was developed to study the pattern of DNA synthesis in the rat lens epithelium after in vivo exposure to UV radiation in the 300 nm wavelength region. It was found that UV radiation (peak transmission = 298 nm, half-width = +/- 10 nm) induces unscheduled DNA synthesis and that the proportion of nuclei in S-phase concurrently is reduced indicating an inhibition of the scheduled DNA synthesis. The registered unscheduled DNA synthesis is believed to be excision repair of DNA damage induced by the UV radiation. Excision repair in lens epithelial cells could be one mechanism involved in the correlation between exposure to sunlight and cataracts.

Animals↗
PubMed1986

Plasma and erythrocyte concentrations of mercaptopurine after oral administration in children.

Plasma and erythrocyte concentrations of 6-mercaptopurine (6-MP) were determined by gas chromatography-mass spectrometry. Eleven children (9 with acute lymphatic leukemia) were studied after oral intake of 6-MP doses ranging between 31 and 128 mg/m2 body surface area. The concentrations of 6-MP in plasma were found to vary considerably between patients even after dose normalization to 75 mg/m2. After dose normalization the mean peak plasma concentration was 0.68 microM (range 0.12-1.38) and the area under the plasma concentration-time curve (AUC) was 1.37 microM.h (range 0.12-3.04). The mean time taken to reach the peak concentration was 1.3 h (range 1-2), and the half-life of elimination was 1.8 h (range 0.6-2.5). No patient had detectable 6-MP concentrations 12 h after dose intake. The concentrations of 6-MP tended to be higher in erythrocytes than in plasma. The mean peak concentration in erythrocytes was 131% and the AUC 145% of that found in plasma. The mean half-life of elimination from erythrocytes was 2.0 h (range 0.7-2.8). These data indicate that 6-MP can pass through all membranes rapidly to reach intracellular concentrations equal to or even higher than in plasma. In summary, marked interindividual differences in pharmacokinetics were found, probably due to highly variable bioavailability of oral 6-MP. Further studies are needed to determine whether measurements of plasma concentrations of 6-MP can be used to optimize maintenance treatment of childhood leukemia.

Administration, Oral↗
PubMed1985

Is 125I iothalamate an ideal marker for glomerular filtration?

The triiodinated angiographic contrast medium, iothalamate, has (usually labelled 125I) been used extensively as a marker for glomerular filtration. We have studied the renal handling of 125I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51Cr-EDTA (EDTA) at 37 degrees C; a difference that was abolished at 0 degree C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice (P less than 0.05) that of EDTA (CEDTA) or 3H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1% (P less than 0.01; N = 10). After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced (P less than 0.01) and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% (P less than 0.01) before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% (P less than 0.05) by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% (P less than 0.005) and 22% (unchanged) for PAH and EDTA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Determination of chloroquine and its desethyl metabolite in whole blood: an application for samples collected in capillary tubes and dried on filter paper.

A high performance liquid chromatography method for analysis of chloroquine and desethylchloroquine was adapted for 75 microliters aliquots of whole blood obtained by finger-prick and dried on filter paper. The precision of the method was satisfactory at whole blood concentrations of 40 nmol/L (coefficient of variation, 5%). The dried samples were stable for at least 7 weeks at 20 degrees C. The concentrations in venous whole blood and in dried samples correlated well. The correlation coefficient was 0.99 for chloroquine and 0.97 for desethylchloroquine. Chloroquine concentrations were marginally but significantly higher in venous whole blood. When fitted to a linear equation (y = bx + a) the relationship was y = 0.96x + 0.03. Desethylchloroquine concentrations did not differ significantly in venous whole blood and in finger-prick blood dried on filter paper. The method is specific and sensitive enough for pharmacokinetic studies and can be used in areas with limited technical facilities.

Blood Specimen Collection↗
PubMed1985

Chloroquine and desethylchloroquine in plasma, serum, and whole blood: problems in assay and handling of samples.

A spectrophotofluorometric method for determination of chloroquine in body fluids was compared with a recently developed high performance liquid chromatographic (HPLC) method. The spectrophotofluorometric method was found to codetermine the main metabolite desethylchloroquine and thus to give higher "chloroquine" concentrations than the HPLC method. The concentrations determined with spectrophotofluorometry roughly corresponded to the calculated sum of chloroquine and desethylchloroquine as determined with the HPLC method. The concentrations of chloroquine and desethylchloroquine were higher in serum, and considerably higher in whole blood, than in plasma. The duration and force of centrifugation greatly influenced the concentrations of chloroquine and desethylchloroquine found in plasma. The concentrations decreased as centrifugal force increased reaching relatively stable levels at 500 g. Increasing the centrifugation time partly compensated for lower g forces. These methodological problems can be avoided by using whole blood for determinations of chloroquine. Since the biological activities of desethylchloroquine and chloroquine are not the same, drug monitoring should be performed with a method distinguishing between the parent drug and the metabolite.

Blood Specimen Collection↗
PubMed1984

Pharmacokinetics of cimetidine in advanced cirrhosis.

The effect of impaired liver function on the pharmacokinetics of cimetidine was studied in 8 patients with advanced cirrhosis given single doses of 100 mg i.v. and 400 mg p.o. on separate days. Compared to a control group of 10 healthy volunteers, the total renal and nonrenal clearance was significantly reduced in the cirrhotic patients; (total plasma clearance mean +/- SD) 356 +/- 181 vs 789 +/- 262 ml/min (p less than 0.01); renal clearance (Clr) 296 +/- 100 vs 588 +/- 181 ml/min (p less than 0.01) and nonrenal clearance ( Clnr ) 97 +/- 111 vs 205 +/- 89 ml/min (p less than 0.05). Compared to published results for age-matched ulcer patients, both total and nonrenal clearance were lower whereas renal clearance was within the reported normal range. A significant reduction in volume of distribution (Vd beta) was found, from 2.1 +/- 0.1 l/kg in controls to 1.0 +/- 0.4 l/kg, and in the patient group there was a significant correlation between Vd beta and total plasma clearance (r = 0.72, p less than 0.05). Volume of distribution in steady state (Vdss) did not differ from published results in age-matched controls. No significant change in half-life was found. Bioavailability, estimated by AUC-measurement, showed considerable patient variability (21-143%), with a mean of 70 +/- 39%. This was lower than in the controls. In contrast, measurement of urinary excretion showed higher bioavailability in the patients (66 +/- 23 vs 51 +/- 8%). No correlation was found between any of the kinetic parameters and the clinical and laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Steady state pharmacokinetics of trimethoprim 300 mg once daily in healthy volunteers assessed by two independent methods.

The steady state pharmacokinetics of trimethoprim was determined after 300 mg orally once daily to 6 healthy volunteers for 9 days. The microbiological assay of plasma level was unreliable at trimethoprim concentrations greater than 4 micrograms/ml, so results from an HPLC-assay are given. Steady state was present after 3 days. The plasma concentration peaked 1 to 4 h (mean 2.0 h) after the dose at a mean of 6.0 micrograms/ml (range 3.1-9.5 micrograms/ml); the minimum value was 1.5 micrograms/ml (range 0.6-2.9 micrograms/ml). The mean AUCss was 77 micrograms/ml X h and the mean plasma clearances was 67 and 74 ml/min on Days 8 and 9. Renal clearance was about 60% of the plasma clearance. The average plasma half life was 10.6 h (range 8.7-15.3 h). Thus, there was considerable interindividual variation in all pharmacokinetic parameters. 72 h after the last dose trimethoprim was detectable in plasma in only 1 of the 6 subjects. The minimum urinary concentration of trimethoprim during treatment was always well above (range 22 to 220 micrograms/ml) the MIC values for most urinary tract pathogens. Therefore, a daily dose of 300 mg trimethoprim results in a therapeutic concentration in urine at steady state that lasts throughout the dosing interval and in most subjects probably lasts also for a further 24 h. Trimethoprim administration raised mean serum creatinine from 67 to 97 mumol/l, probably due to competitive inhibition of the tubular secretion of creatinine.

Adult↗
PubMed1984

Dose, plasma concentration, and effect of oral terbutaline in long-term treatment of childhood asthma.

Oral terbutaline in gradually increasing doses from 45 to 166 micrograms/kg three times daily was administered to asthmatic school children. There was a linear relationship between dose and steady-state plasma concentration of terbutaline within patients, but the plasma levels varied fourfold between patients taking similar doses. The consumption of beta 2-stimulants in aerosol form decreased, and the symptom score, peak expiratory flow rate, and FEV1 improved during treatment with a roughly linear dose-effect relationship. Significant increases in pulse rate and skeletal muscle tremor were also measurable. There was no clear correlation between plasma levels of terbutaline and reported side effects. Linear regression analysis revealed a statistically significant relationship between bronchodilatation and the same plasma level was considerable. Determination of the plasma terbutaline concentration therefore seems to be of limited value in clinical practice. Instead, the dose should be individualized on the basis of clinical effect and tolerance. Our data indicate that many young asthmatic children will tolerate and sometimes benefit from higher doses than are generally recommended if they are carefully titrated with stepwise increments.

Administration, Oral↗
PubMed1984

Influence of anaesthesia on blood flow to the calves during surgery.

The blood flow to the calves during abdominal surgery under different kinds of general anaesthesia was measured by strain gauge plethysmography in 12 patients. The volume flow increased 100% during surgery in both light and deep anaesthesia, caused by a decrease in peripheral resistance. The increase in volume flow could partly be explained by the anaesthesia itself, possibly induced by the use of a nitrous oxide-oxygen gas mixture. The surgical procedure caused a further increase in volume flow. Possible underlying mechanisms are discussed.

Adult↗
PubMed1984

Oral terbutaline in chronic childhood asthma; effects related to plasma concentrations.

Nine children, 10-15 years old with chronic asthma, were treated for weekly periods with gradually increasing doses of oral terbutaline sulphate: 45, 79, 118 and 166 micrograms/kg (mean values) 3 times daily. There was a linear relationship between dose and steady-state plasma concentration of terbutaline within patients, but the plasma levels varied 3-fold between patients taking similar doses. Symptom score, peak expiratory flow rate (PEFR) and volume of air expelled in the first second of forced expiration (FEV1) improved with increasing doses, and the need for inhalation therapy decreased. An increase in pulse rate and tremor was measurable at all dose levels, but reported side-effects were few and mild. Linear regression analysis showed a statistically significant relationship between the plasma concentration of terbutaline and the effect on FEV1 (p less than 0.01) and PEFR (p less than 0.05) within patients.

Asthma↗