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Biomedical subjects

J O Svensson

Publications and source records attributed to J O Svensson.

15 recordsLinked to original sources
PubMed1992

Dose-dependent absorption of amoxicillin in patients with an ileostomy.

Amoxicillin was given as single doses of 375, 700, 1500, 3000 and 6000 mg an oral suspension to four volunteers with an ileostomy and with no active intestinal disease after an overnight fast. The excretion of amoxicillin and its penicilloic acid was followed in samples taken from the ileostomy and in urine produced over 6 h. Beta-lactamase activity was measured in ileal fluid and none was found. The percentage of the dose recovered from the ileostomy increased successively from 8% at the lowest dose to 77% at the highest dose. A complementary excretion pattern of amoxicillin was found in the urine, amounting to 70% recovery at the lowest dose to 23% at the highest dose. The results confirm the dose-dependence of the absorption of amoxicillin, which could at least in part be due to specialised absorption of this drug in humans.

Adult↗
PubMed1992

Nonlinearity of amoxicillin absorption kinetics in human.

Specialised gastrointestinal absorption of amoxicillin has been suggested in man and has been demonstrated in animals. In order to study the rate and extent of amoxicillin absorption, six healthy subjects were given 500 mg IV and two oral doses (500 mg and 3 g as a suspension). Absorption kinetics was analysed by compartmental modelling, noncompartmental methods and by calculation of absorption rates using deconvolution. Dose-dependency of the extent of amoxicillin absorption was observed, with a lower than expected mean maximum plasma concentration (49%), and fraction of the dose absorbed (39%) after the 3 g dose calculated from the 500 mg dose, assuming kinetic linearity. Zero-order kinetics of absorption was apparent in some subjects after the 500 mg dose, both from model fitting and absorption rate profile. However, no pattern consistent with pure first-order or zero-order absorption was observed after both oral doses in any individual. The dose-dependency of amoxicillin absorption was confirmed by a trend to an increased time of absorption for the high dose. The results show the variable nature and nonlinearity of the gastrointestinal absorption of amoxicillin and indicate the involvement of a number of factors, in addition to simple diffusion.

Amoxicillin↗
PubMed1992

Bioavailability of two Soviet sustained-release theophylline formulations in comparison with TheoDur.

The pharmacokinetic parameters of two theophylline preparations of Soviet origin (Theobiolongas and Theopaek) were compared with the reference preparation TheoDur. The three sustained-release preparations were administered in a single oral dose (400 mg) to healthy volunteers. Blood samples were drawn over 36 hr and plasma concentrations of theophylline were measured by HPLC. Significant differences in the pharmacokinetic parameters were observed between the drugs. Compared to TheoDur, the two Soviet drugs, Theobiolongas and Theopaek, had lower bioavailability (86% and 82%, respectively), and higher rate of absorption. An 8-hr dosing interval should be preferred for Theobiolongas and Theopaek while twice-daily administration appears to be appropriate for these preparations only in exceptional cases.

Administration, Oral↗
PubMed1992

Different regiospecificity in the hydroxylation of the antidepressant desmethylimipramine between rat brain and liver.

Incubation of the tricyclic antidepressant desmethylimpramine (DMI) with rat liver or brain microsomes in the presence of NADPH or t-butyl-hydroperoxide (TBH) revealed different regiospecificities in the hydroxylation reactions between the tissues. In brain preparations 10-OH-DMI was formed in reactions supported by NADPH or TBH, whereas in the latter case also an unidentified metabolite could be detected. Inclusion of exogenous NADPH-cytochrome P450 reductase in the brain preparations caused a 10-fold higher rate of 10-hydroxylation but no 2-OH-DMI could be detected. By contrast, liver microsomal preparations in the presence of NADPH catalyzed formation of both 2- and 10-OH-DMI, whereas only 10-OH-DMI was formed in TBH-supported reactions. The results indicate that antidepressant drugs can be metabolized in brain with different stereospecificity as compared to liver.

Animals↗
PubMed1991

Single-dose and steady-state kinetics of morphine and its metabolites in cancer patients--a comparison of two oral formulations.

The single-dose and steady state kinetics of morphine given as controlled-release tablets (30 mg every 12 h) and as a solution (15 mg every 6 h) have been compared in 11 cancer patients with chronic pain. The concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were analyzed by HPLC. There were no significant differences between the tablets and solution in the mean steady state concentrations of morphine, M3G or M6G. The tmax was 3.3 h for the tablets compared to 1.1 h for the solution. After giving the controlled-release tablets every 12 h there was a significantly higher fluctuation index of the morphine concentrations than after the solution. Urinary recovery at steady state was comparable between the two preparations, with averages of 57% and 47%, respectively. Thus, no major differences were found in the pharmacokinetics of morphine and its glucuronidated metabolites after 30 mg morphine as controlled-release tablets every 12 h or 15 mg of morphine solution every 6 h, except for a significantly longer tmax and greater fluctuation in morphine concentrations after the controlled-release tablets.

Adenocarcinoma↗
PubMed1991

Pharmacokinetics of codeine and its metabolites in Caucasian healthy volunteers: comparisons between extensive and poor hydroxylators of debrisoquine.

1. The kinetics of codeine and seven of its metabolites codeine-6-glucuronide (C6G), norcodeine (NC), NC-glucuronide (NCG), morphine (M), M-3 (M3G) and 6-glucuronides (M6G), and normorphine (NM) were investigated after a single oral dose of 50 mg codeine phosphate in 14 healthy Caucasian subjects including eight extensive (EM) and six poor (PM) hydroxylators of debrisoquine. The plasma and urine concentrations of codeine and the metabolites were measured by h.p.l.c. 2. The mean area under the curve (AUC), half-life and total plasma clearance of codeine were 1020 +/- 340 nmol l-1 h, 2.58 +/- 0.57 h and 2.02 +/- 0.73 l h-1 kg-1, respectively. There were no significant differences between EM and PM in these aspects. 3. PM had significantly lower AUC of M3G, the active metabolites M6G, NM and M (P less than 0.0001), and lower partial metabolic clearance by O-demethylation (P less than 0.0001). In contrast, the PM had higher AUC of NC (P less than 0.05) than the EM. There was no difference between PM and EM in the AUC of C6G and NCG, nor in the partial clearances by N-demethylation and glucuronidation. 4. Among EM, the AUC of C6G was 15 times higher than that of codeine, which in turn was 50 times higher than that of M. The AUCs of M6G and NM were about 6 and 10 times higher than that of M, respectively. The partial clearance by glucuronidation was about 8 and 12 times higher than those by N- and O-demethylations, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

A comparison of the pharmacokinetics of codeine and its metabolites in healthy Chinese and Caucasian extensive hydroxylators of debrisoquine.

1. The kinetics of codeine and metabolites were studied in eight unrelated healthy Chinese subjects following a single oral dose of 50 mg codeine phosphate. The data were compared with those from eight Caucasian subjects who were matched with the Chinese group according to their metabolic ratio (MR) of debrisoquine. 2. Mean values of Cmax (445 nmol l-1) and AUC (1660 nmol l-1 h) of codeine in the Chinese were significantly higher than those in the Caucasians (292 nmol l-1 and 1010 nmol l-1 h). Thus plasma clearance was significantly lower (P less than 0.02) and the plasma half-life was longer (P less than 0.05) in the Chinese. 3. Partial clearance by glucuronidation was significantly lower (0.79 +/- 0.14 s.d. vs 1.42 +/- 0.48 s.d. 1 h-1 kg-1) in Chinese than in Caucasians. 4. The total urinary recovery of drug-related material in 48 h urine was similar in Chinese (82.2%) and Caucasians (84.4%). The recovery of unchanged codeine was significantly higher in Chinese (5.7%) than in Caucasians (3.3%). 5. The AUC ratios of codeine relative to its 6-glucuronide, morphine and norcodeine were 1:9, 35:1 and 4:1, respectively in Chinese. The corresponding ratios in Caucasians were 1:15, 50:1 and 6:1. 6. There was no significant difference between Chinese and Caucasians in the renal clearances of codeine and its primary metabolites. 7. Large interethnic differences in the kinetics of codeine have been shown. The Chinese are less able to metabolise codeine mainly because of a lower efficiency in glucuronidation.

Administration, Oral↗
PubMed1991

Upper gastrointestinal bleeding. With special reference to blood transfusion.

Upper gastrointestinal haemorrhage in 978 unselected patients during a 9-year period was reviewed in regard to incidence, diagnosis, treatment and mortality rate. The annual incidence was 1/1,000 of the catchment population. The source of bleeding was established in 89% of cases. Peptic ulcer accounted for 53% of total admissions. Blood transfusion was given only when the haemoglobin was less than 8.0 g/dl or if the patient was in shock. Emergency surgery was performed on only 31 patients (3%). The perioperative mortality was 13% and the overall mortality 6%. It is concluded that current treatment policy resulted in low rates of operation and mortality in these unselected cases of upper gastrointestinal haemorrhage. The results support the theory that a hypercoagulable state in gastrointestinal bleeding is counteracted by citrated stored blood.

Aged↗
PubMed1990

Carbamazepine-10,11-epoxide in epilepsy. A pilot study.

The effects of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, were evaluated in seven outpatients with frequent epileptic seizures. The study included an initial 4-week period with the carbamazepine dose optimized for each patient. Patients were then crossed over, dose by dose, to carbamazepine-10,11-epoxide and followed up for another 4 weeks. Dosing was single blind. The evaluation of the anticonvulsant effect was hampered by marked fluctuations in plasma levels during treatment with carbamazepine-10,11-epoxide. There was, however, no significant change in seizure control. During epoxide treatment, no subjective side effects were reported despite epoxide plasma concentrations up to 57 mumol/L. Neuropsychological assessment revealed a significant improvement in finger motor speed and logical reasoning during the carbamazepine-10,11-epoxide period. Subnormal serum sodium levels in two patients were normalized after switching from carbamazepine to the epoxide. Continued investigations with this active metabolite of carbamazepine in epilepsy are therefore justified.

Adult↗
PubMed1990

The metabolism and bioavailability of morphine in patients with severe liver cirrhosis.

1. The oral and intravenous kinetics of morphine were investigated in seven cirrhotic patients with a history of encephalopathy. The plasma concentrations of morphine and its metabolites morphine-3 (M3G) and morphine-6 (M6G) were measured by h.p.l.c. 2. The mean terminal elimination half-life of morphine was 4.2 h (95% CI 3.6-4.8) the mean volume of distribution was 4.1 l kg-1 (95% CI 2.9-5.4) and the mean plasma clearance was 11.4 ml min-1 kg-1 (95% CI 8.1-14.7). The mean oral bioavailability was 101% (95% CI 56-147). 3. The plasma clearance of morphine was significantly lower, its terminal elimination half-life longer and its oral bioavailability greater in the cirrhotic patients compared with patients with normal liver function. The metabolic ratio M3G/morphine was significantly lower in the cirrhotic patients than in control subjects after oral dosing, but did not differ after intravenous dosing. 4. The average urinary recoveries of morphine plus M3G and M6G were 49.9% after i.v. and 57.7% after oral administration. There were no statistically significant differences in the urinary recovery between the two routes of administration or between the cirrhotic patients and controls. 5. Specific changes in the EEG pattern could not be detected after intravenous dosage. 6. The metabolism of morphine is impaired significantly in patients with severe cirrhosis. Clinically important findings were a high oral bioavailability and a long elimination half-life. These findings call for cautious dosing of oral and intravenous morphine in patients with severe end stage liver disease.

Administration, Oral↗
PubMed1979

Changing pattern in aetiology of pancreatitis in an urban Swedish area.

Two groups of patients admitted with a first attack of acute pancreatitis are reviewed. The first group, consisting of 105 patients, was admitted between 1968 and 1969; the second group of 204 patients was admitted between 1974 and 1975. These groups were compared with one of 454 patients admitted between 1956 and 1960 whose details were published earlier by our unit (Edlund et al., 1968). The aim of this study was to determine whether the incidence of factors associated with pancreatitis within the population of the city of Göteborg had changed in the 20-year period. In the 1956--60 group gallstone disease was the main associated factor (68 per cent), but in the later groups alcohol-induced pancreatitis assumed the leading role (68 and 66 per cent respectively). Alcohol-induced pancreatitis tended to occur at a younger age than gallstone pancreatitis. Thirty-one per cent of 449 patients admitted with an acute attack of alcoholic pancreatitis in the two last periods of study had had previous attacks.

Acute Disease↗
PubMed1979

Total small bowel strangulation: a case report.

A case of strangulation of the entire small intestine caused by an internal incarcerated hernia is presented. At laparotomy the small intestine was severely discoloured, paralytic and the viability of the bowel was questionable. No resection was performed. At a second laparotomy 10 h later the intestine was hyperaemic and exhibited lively motor activity. Recovery was complete. The importance of prolonged conservative management in avoiding extensive resection is stressed.

Adult↗
PubMed1975

Role of intravenously infused insulin in treatment of acute pancreatitis. A double-blind study.

The effect of insulin treatment in acute pancreatitis was studied in a double-blind investigation. Fifteen patients with clinical signs of acute pancreatitis were treated with intravenous infusion of glucose and insulin only. Twelve patients were free from pain within four hours of commencement of treatment. Within eight hours all fifteen were free from abdominal pain. Fourteen patients with pancreatitis established by the same criteria were treated with glucose infusions without insulin. Only four of the patients in this group became free from pain within four hours. The role of intravenously infused insulin with respect to the more beneficial effect in the first group is discussed.

Acute Disease↗