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Biomedical subjects

R A Walstad

Publications and source records attributed to R A Walstad.

At least 37 records · Page 2Linked to original sources
PubMed1987

The concentrations of ceftazidime and thiopental in maternal plasma, placental tissue and amniotic fluid in early pregnancy.

Studies on the transfer of drugs from mother to fetus in the first trimester of pregnancy are important because of the possible teratogenic effect on the fetus as well as possible therapeutic effect on both sides of the feto-maternal barrier. The purpose of this study was to measure drug concentrations in maternal plasma, placental tissue and amniotic fluid in a group of first-trimester abortion patients. Ceftazidime and thiopental were chosen as experimental drugs. The analyses were done with high pressure liquid chromatography. The penetration of ceftazidime into placental tissue and amniotic fluid was 20.6 and 2.2% from 1 to 4 h after drug administration. The corresponding values for thiopental were 54.3-71 and 1.5-7.4% from 5 to 15 min after drug administration, indicating a rapid transfer of both drugs across the feto-maternal barrier during this period in pregnancy.

Abortion, Induced↗
PubMed1987

The penetration of ceftazidime into the inflamed rabbit eye.

Acute endophthalmitis was unilaterally induced in 8 rabbits by intravitreal injection of 5 micrograms Escherichia coli endotoxin. A reproducible increase in aqueous humour polymorphonuclear neutrophils and total protein content was observed after 24 h (mean +/- SD: 2400 +/- 274 X 10(6)/l and 3.7 +/- 0.4 g/l, respectively). In the opposite eye only minor changes occurred, making it suitable as a paired control. The intraocular penetration of ceftazidime was then studied in 30 rabbits after i.v. injection of 50 mg/kg body weight. The mean penetration into aqueous humour of the eyes with and without endophthalmitis was 64 and 10%, respectively. In the vitreous body the corresponding penetration was 5 and 1%. The concentration of ceftazidime achieved in the intraocular structures was sufficient to inhibit the growth of pathogens, i.e. Enterobacteriaceae, commonly responsible for intraocular infections.

Animals↗
PubMed1986

Pharmacokinetics of ceftazidime in patients with biliary tract disease.

After administration of ceftazidime as a 1 g i.v. bolus injection, its concentration was measured by HPLC at frequent intervals in serum, bile and tissue from different parts of the biliary tract in 32 patients undergoing operation for biliary tract disease. In bile from the functioning gallbladder and common bile duct, a high concentration of ceftazidime was found, mean 18.5 and 26.6 mg/l, respectively. In bile from the non-functioning gallbladder, a very low concentration was found (less than 1.5 mg/l). Ceftazidime in the gallbladder wall varied considerably with the type and degree of inflammation judged histologically; the mean level was 21.3 mg/kg. The elimination half-life of ceftazidime was 1.74 h, apparent volume of distribution 20.01 and total plasma clearance 133 ml/min. In bile from T-tube specimens a high concentration was found, the mean peak values being 27.2 mg/l. However, biliary excretion of the drug was low at less than 0.5% of the administered dose. These concentrations of ceftazidime were sufficient to inhibit the in-vitro growth of pathogens, namely the Enterobacteriaecae commonly responsible for biliary tract infection.

Adult↗
PubMed1986

Pharmacokinetics and tissue penetration of Timentin: a simultaneous study of serum, urine, lymph, suction blister and subcutaneous thread fluid.

Following iv bolus injection of 3.2 g Timentin (ticarcillin 3.0 g plus clavulanic acid 0.2 g) to 12 volunteers, the antibiotic concentrations were analysed by HPLC methods in serum, urine and fluids from subcutaneous threads, suction blisters and lymph during 8 h. Pharmacokinetic parameters, urine recovery, penetration and ticarcillin/clavulanic acid ratios were calculated. The antibiotic concentration in thread fluid closely followed the serum concentration. For ticarcillin the mean (+/- S.D.) elimination half-lives in serum and thread fluid were 1.0 +/- 0.1 and 1.2 +/- 0.1 h, respectively. For clavulanic acid the half-lives in these fluids were 0.9 +/- 0.1 and 1.0 +/- 0.1 h. The lymph and blister fluid concentration followed a similar pattern, but differed from those in serum, the mean (+/- S.D.) elimination half-lives for both compounds ranging from 1.1 +/- 0.2 to 3.2 +/- 0.3 h. The urine recovery of ticarcillin was 86% and of clavulanic acid 51% of the administered dose. The penetration of clavulanic acid into the different tissue fluids was superior to ticarcillin, ranging from 78 to 88% for clavulanic acid and 52-70% for ticarcillin. The concentration ratios of the two compounds, being 15:1 at the time of injection, varied widely in the different tissue fluids with time. This was also the case with AUC(0-infinity) ratios. A relative decrease of clavulanic acid was observed, most pronounced in serum and thread fluid. However, the antibiotic concentrations achieved in serum, urine and extravascular fluid should be adequate in most infections caused by a wide range of clinically important pathogens.

Adult↗
PubMed1986

Self-poisoning with theophylline. The effect of repeated doses oral charcoal on drug elimination.

A heavy smoking male patient with moderate to severe theophylline poisoning is presented. Repeated doses of oral charcoal were given in addition to usual supportive treatment. During this treatment the elimination half-life of the drug (T1/2) was 2 hours. The toxic symptoms disappeared rapidly when the serum concentration was reduced to the therapeutic concentration range. T1/2 was approximately 24 hours in the same patient in a steady state study without oral charcoal treatment. Repeated doses of oral charcoal seem to increase theophylline elimination and should be administered in moderate to severe theophylline poisoning in addition to the usual supportive treatment and correction of metabolic disturbances.

Charcoal↗
PubMed1985

The influence of sustained release theophylline therapy on free fatty acids in serum.

The serum concentrations of theophylline, total free fatty acids (FFA) and subgroups were studied in ten healthy volunteers treated with sustained release theophylline twice daily during 9 days. Analyses were performed before and on day 1, 4 and 9 of treatment. Mean theophylline serum levels within the therapeutic range were obtained during the study, ranging from 62 +/- 7 to 82 +/- 10 mumol/l. The mean serum concentrations of total FFA and subgroups increased significantly during treatment, showing the highest levels on day 4. Comparing fasting total FFA concentrations, an increase of 123% and 48% from pretreatment levels were found on day 4 and 9, respectively. The subgroups were influenced to a different degree by theophylline intake. Arachidonic acid (20:4) was not increased, while among the others, saturated FFA increased less than the unsaturated.

Adult↗
PubMed1985

Penetration of ceftazidime into the normal rabbit and human eye.

The penetration of ceftazidime into the aqueous humour and the vitreous body of the rabbit eye, after intravenous (i.v.) bolus or subconjunctival injection, was investigated. A dose of 50 mg/kg body weight was administered. After i.v. administration the mean penetration into the aqueous humour was 13% of the plasma values. After subconjunctival injection into the left eye, mean levels of 14% and 25% of the plasma concentrations were found in the right and left eye, respectively. The concentrations in the vitreous body were in all cases below the ceftazidime detection limit (1 mg/l), i.e. less than 1% of the plasma levels. The mean penetration of ceftazidime into human aqueous humour (measured during cataract extraction) was 19% after 2 g i.v. bolus injection. Ceftazidime levels sufficient to inhibit the growth of most pathogens commonly responsible for intraocular infections, including Pseudomonas spp., were consistently found in the aqueous humour. However, inadequate concentrations were achieved in the vitreous body.

Aged↗
PubMed1985

Long-term therapy with sustained-release theophylline.

Twenty patients with partially reversible bronchial obstruction due to chronic obstructive lung disease participated in a study comparing serum levels, clinical and side-effects of a sustained-release formulation of theophylline with placebo. Prior to the study, theophylline dosages were individually adjusted to give serum levels of 55 to 75 mumol/l 4 hours after tablet intake. Theophylline or placebo was then administered every 12 hours with crossover after 6 weeks. During the study, patients were examined in the morning every second week and lung function tests carried out before and after salbutamol inhalation. Doses required to achieve the desired serum concentration showed great inter-individual variations, but the obtained levels were stable during the whole study. Lung function tests were significantly better in the theophylline period. After inhalation of salbutamol, values were also better in the theophylline period but the differences were less marked and of no statistical significance. Subjective improvement from theophylline was not observed. Side-effects reported were mild and caused no withdrawals.

Adult↗
PubMed1985

Steady state pharmacokinetics of tiaprofenic acid in elderly patients.

Tiaprofenic acid (Surgam) steady state pharmacokinetics was investigated in eight elderly patients with three different dosage regimens: 200 mg twice daily, 400 mg twice daily and 200 mg three times daily. The following dose independent pharmacokinetic parameters were evaluated from a two-compartment open model; absorption lag time: 0.23 +/- 0.08 h, absorption rate constant: 4.32 +/- 0.51 h-1, distribution rate constant: 1.31 +/- 0.13 h-1 and elimination half-life: 4.66 +/- 0.42. An increase in dose produced a significant and proportional increase in tiaprofenic acid peak and trough serum concentrations at steady state. In contrast to the above mentioned dose independent parameters, the area under the serum concentration-time curve showed a small (12%), but significantly higher increase than expected when the dosage regimen was increased from 200 mg X 2 to 400 mg X 2. This was, however, considered to be of no clinical relevance. Anticipating a 19% reduction of tiaprofenic acid bioavailability due to the intake of food, approximations of total body clearance and apparent volume of distribution can be made to 30.0 +/- 2.0 ml/min and 11.8 +/- 2.0 l, respectively. In spite of the small disproportional increase (12%) observed in the area under the serum concentration-time curve, it can be concluded that tiaprofenic acid shows a well defined pharmacokinetics in old people with acceptable interindividual variations and with a fast building-up to constant and predictable steady state levels within the dosage regimens investigated. A linear relationship was demonstrated between creatinine clearance and tiaprofenic acid total body clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Penetration of erythromycin in respiratory tract infections.

Successful treatment of respiratory tract infections with erythromycin may depend upon adequate penetration of the drug to the site of infection. The delivery of antibiotics into respiratory tract secretions is a simple passive diffusion process along a concentration gradient according to Fick's principle. A number of other factors including physicochemical characteristics of the drug and host defence mechanisms may further modify the tissue penetration. A common feature of penetration studies in respiratory tract infections is the wide range of results. This is due to the numerous variables involved in this kind of study. However, the studies performed at steady state, and after oral administration of erythromycin, show a rapid increase in drug concentrations in adenoid and tonsillar tissue homogenates and sustained levels equal to or higher than in serum. In secretions of the middle ear, paranasal sinuses and bronchiae the penetration and elimination of erythromycin is much slower. The drug levels were equal to--or in some cases even higher than--steady state serum concentrations. Fluctuations, however, were less pronounced. In lung tissue homogenates erythromycin concentrations higher than the serum levels have generally been found. In respiratory tract secretions and tissues the penetration of erythromycin is good. Sufficient levels are reached to inhibit in vitro the growth of most common pathogens involved in respiratory tract infections with the exception of some strains of Haemophilus influenzae.

Bacterial Infections↗
PubMed1983

Pharmacokinetics and clinical effects of cefuroxime in patients with severe renal insufficiency.

The pharmacokinetics and clinical effects of cefuroxime were investigated in 5 patients with severe impairment of renal function (creatinine clearance less than or equal to 23 ml/min), suffering from an urinary tract infection. Bolus i.v. injections of cefuroxime 750 mg b.i.d. or 750 mg once daily were given to the patients depending on the degree of renal impairment. The concentration of drug in serum and urine was measured during treatment, and pharmacokinetic parameters were evaluated on the second and last days; the parameters obtained on the 2 days did not differ significantly. Drug elimination half-life increased from 4.2 h (creatinine clearance 23.0 ml/min) to 22.3 h (creatinine clearance 5.0 ml/min) with decreasing renal function. The apparent volume of distribution ranged from 11.6 to 17.9 l, and showed a substantial increase to 29.6 l in the patient with the poorest renal function. A linear correlation was found between the total and renal clearance of cefuroxime and the creatinine clearance; the extrarenal clearance was 8.24 ml/min. Concomitant treatment with furosemide did not impair renal function and no evidence of nephrotoxicity was found. The clinical efficacy of the drug was good. Symptoms of infection subsided after 3-4 days and the isolated pathogens were eradicated. No relapse or episodes of reinfection were observed in a following-up period of 3 months. The drug was well tolerated and no side effects or changes in haematological or biochemical values were seen.

Aged↗
PubMed1983

The evaluation of ceftazidime in the treatment of bacterial infections in eighty seriously ill patients.

Eighty patients with suspected or diagnosed bacterial infections were treated with ceftazidime. Sixty-five patients with 88 sites of infections could be assessed clinically. A cure or improvement was achieved in 61 patients (94%) with a total of 83 infection sites (94%). Failures were seen in four critically ill patients with severe underlying diseases. Eighty-six pathogens, most frequently Enterobacteriaceae, were isolated from appropriate specimens. The infecting organisms were all eradicated during therapy. In two patients reinfection with a new strain occurred. Except for a severe anaphylactic reaction in one patient, ceftazidime was well tolerated.

Adolescent↗
PubMed1983

Pharmacokinetics and tissue penetration of ceftazidime: studies on lymph, aqueous humour, skin blister, cerebrospinal and pleural fluid.

The elimination kinetics and penetration of ceftazidime into skin blister and lymphatic fluid were studied in nine healthy volunteers following a 1 g iv bolus injection. From the concentration time curve in plasma the following pharmacokinetic parameters (mean +/- S.D.) were calculated: elimination half-life 1.85 +/- 0.33 h; area under the curves 127 +/- 12 mg . h/l; apparent volume of distribution: 21.1 +/- 2.61; total plasma clearance: 133 +/- 13 ml/min and renal clearance: 109 +/- 7 ml/min. Urine recovery after 8 h was 82% of the administered dose. Nearly the same elimination rate constant, half-life and area under the curve were demonstrated for blister fluid and lymph. The penetration of ceftazidime into cerebrospinal fluid (n = 19), aqueous humour (n = 21) and pleural effusions (n = 5) were studied in patients after a 2 g iv bolus injection. In patients with normal meninges (n = 14) the penetration was poor: the concentrations were less than 1 mg/l. In patients with meningitis (n = 5) levels of 18, 17, 16, 1 and 0.8 mg/l were found. Aqueous humour penetration was satisfactory, and a mean concentration of 11 +/- 4 mg/l corresponding to a penetration ratio of 19% was found. The penetration of ceftazidime into large pleural effusions was also good with concentrations from 17 +/- 3 to 28 +/- 2 mg/l, corresponding to a mean penetration ratio of 38%.

Adult↗
PubMed1983

The pharmacokinetics and diuretic effects of piretanide in chronic renal insufficiency.

The pharmacokinetics of piretanide, a new loop diuretic, were studied in four patients with GFR 4.7-14.8 ml/min. An oral dose of piretanide 18 mg was given at 08.00 h in two patients and at 08.00 h and 14.00 h in two. Blood samples were drawn after 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. Serum concentrations of piretanide were estimated by radioimmunoassay. The peak serum concentration of piretanide (1-2 h after drug administration) was 510-880 ng/ml, independent of renal function. Elimination half life (t1/2) was 1.2-4.1 h, area under the curves (AUC(0,24)) 1.63-2.44 micrograms ml-1 h, volume of distribution (Vz) 0.30--0.741#kg, total plasma clearance (CL) 122.8-184.0 ml/min and renal clearance (CLR) 1.5-5.2 ml/min. The clinical effects of oral treatment with piretanide 18 mg twice daily were compared with bumetanide 3 mg twice daily in eight patients with renal failure (GFR 2.2-24.5 ml/min). Both drugs equally increased the 24 h output of urine (delta V), sodium (delta UNaV), chloride (delta UC1V), potassium (delta UKV) and calcium (delta UCaV). Fractional excretion of sodium (ENa%) was doubled by piretanide in patients with GFR less than 8 ml/min while a five fold increase was found in patients with GFR greater than 8 ml/min. The onset of effect was the same for both drugs, but the duration exceeded 6 h only for piretanide. Both drugs were most effective on the first of two consecutive treatment days. Delta UC1V was always greater than delta UNaV and urinary phosphate excretion was unchanged, as expected of a loop diuretic without significant proximal effects. Metabolic or clinical side effects were not noticed.

Bumetanide↗
PubMed1983

The influence of antacid on the absorption of two different sustained-release formulations of theophylline.

Twelve healthy volunteers were treated with two different sustained-release formulations of theophylline (Nuelin Depot 350 mg and Theo-Dur 300 mg) twice daily in an open cross-over study. The serum levels in steady state without and with concomitant administration of antacid were studied. Antacid did not influence the serum theophylline levels in the Theo-Dur treatment period, while in the Nuelin Depot treatment period antacids caused a significantly larger increase in serum levels of theophylline after drug intake. The difference between morning and peak concentrations were also much higher with the combination Nuelin Depot/antacid. This implies that physicochemical factors such as gastrointestinal fluid pH might influence the degradation and/or absorption of some slow-release theophylline formulations as reflected in serum concentrations, and thereby contribute to the therapeutic and side effects of such drugs.

Absorption↗
PubMed1982

Labetalol in the treatment of hypertension in patients with normal and impaired renal function.

Labetalol (Trandate) is a new antihypertensive agent with both alpha- and beta-adrenoceptor blocking properties. In a double-blind cross-over study the antihypertensive action and side-effects of labetalol and propranolol were compared in 18 previously untreated outpatients with hypertension, WHO stage I--III. Mean daily dose of labetalol was 667 mg and of propranolol 129 mg. Labetalol reduced systolic and diastolic blood pressure in the seated and upright position significantly more than propranolol. The pulse rate reduction was greater with propranolol. Side-effects were more pronounced with propranolol. The antihypertensive effect, effect on pulse rate and pharmacokinetics of a single oral dose of 400 mg labetalol were studied in 6 patients with normal and 6 patients with impaired renal function (creatinine clearance less than 20 ml/min), all belonging to WHO stage I--II. A significant fall in pulse rate and systolic and diastolic blood pressure was observed in both groups, the duration being more than 25 h. No difference was found between the two groups. From the serum concentration-time curves the elimination rate constant, elimination half-life and area under the curve were calculated. The mean values of the two groups did not differ significantly. A pronounced interindividual variation was found in both groups.

Adult↗