Interaction of cimetidine and theophylline in two infants.
Explore the source record for details and available documents.
Asthma↗
Biomedical subjects
S M MacLeod
Publications and source records attributed to S M MacLeod.
High-pressure liquid chromatographic assay of cloxacillin in serum and urine.
Two rapid, specific, and sensitive high-pressure liquid chromatographic (HPLC) assays were developed for cloxacillin in serum and urine. A reversed-phase column (RP-8) was selected for use with two different sets of HPLC conditions and sample pretreatment procedures. Cloxacillin extraction efficiencies are reported from serum and urine. Equations are presented for linear relationships between peak height or peak area ratios of cloxacillin to nafcillin (internal standard) and the cloxacillin concentration over a range of 0-80 micrograms/ml. The sensitivity limit of these assays was approximately 0.3 microgram/ml of a standard solution for one method and 0.05 microgram /ml for the other HPLC assay.
Chromatography, High Pressure Liquid↗
High-pressure liquid chromatographic assays for ticarcillin in serum and urine.
Rapid and sensitive high-pressure liquid chromatographic (HPLC) assays for ticarcillin in serum and urine have been developed. Sample pretreatment and optimized chromatographic conditions are presented for a C-18-bonded reversed-phase column used in an internal standard assay method. Ticarcillin has a retention time of or approximately 5.3 min at a flow rate of 1.5 ml/min for a mobile phase of acetonitrile-aqueous 0.06 M sodium biphosphate, pH 2.05, (50.5:100). In a two-step extraction procedure, the ticarcillin extraction efficiencies from serum and urine were 76.1 +/- 4.7 and 80.9 +/- 3.2% respectively. The assay sensitivity limit for ticarcillin in these fluids is approximately 1.0 microgram/ml. A comparison is made of the HPLC and microbiological assay results for ticarcillin in 20 different but equally divided serum samples obtained from two volunteers.
Bacteria↗
Analysis of morphine in serum by high performance liquid chromatography with amperometric detection.
In this report we describe a rapid and sensitive micromethod using high performance liquid chromatography (HPLC) with electrochemical detection (ED) to measure morphine concentration in serum or plasma. The separation of morphine and the internal standard 5-hydroxyquinoline, from interfering compounds present in plasma was achieved by paired-ion reverse phase chromatography using a 70 mM phosphate buffer at pH 5.80. The flow rate was 1 ml/min. Oxidation of morphine and the internal standard was obtained at a potential of 0.60 V. Only 100 microliter of serum or plasma was required. Analytical recoveries for morphine and 5-hydroxyquinoline were determined as 78% and 63% respectively. The between-day precision of serum samples containing 250, 100, and 25 microgram/L of morphine (n = 20) was 6.5%, 5.2%, and 9.5% respectively. The detection limit was determined as 1 microgram/L at a sensitivity of 5 nA/V. In our preliminary studies, 3 children between the ages of 0 and 5 years received a bolus of morphine of 11 microgram/kg, followed by an infusion of 2 microgram/kg/min during surgery. The time-concentration curves demonstrate an initial rapid fall in morphine concentration with subsequent attainment of a steady state concentration of approximately 90 microgram/L after 1 h. This concentration would be expected to produce optimal analgesia in conscious patients.
Child, Preschool↗
Analysis of methotrexate and 7-hydroxymethotrexate by high-performance liquid chromatography and preliminary clinical studies.
The simultaneous analysis of methotrexate (MTX) and its putatively nephrotoxic metabolite, 7-hydroxymethotrexate (7OH-MTX), by high-performance liquid chromatography (HPLC) and ultraviolet spectrophotometric detection is described. Serum extraction employs SEP-PAK C-18 cartridges. Recovery ranges from 78.3 to 84.9% for MTX and 67.6 to 76.1% for 7OH-MTX. Between-day precision studies of serum (controls), containing 2.76 microM MTX and 4.40 microM 7OH-MTX, yielded coefficients of variation of 8.6 and 8.9%, respectively. Reconstitution of the dried residue in 5 mM HCl increases the retention times of 7OH-MTX and MTX, thereby enhancing their separation from extraneous serum peaks. A comparison of MTX levels determined by HPLC and a competitive protein binding assay yielded consistently lower results by HPLC. However, in comparing HPLC to EMIT, two relationships were observed: below 100 microM MTX the methods were in agreement, whereas above 100 microM MTX HPLC again provided lower values. Preliminary pharmacokinetic studies on two patients with osteogenic sarcoma are reported. After receiving 218.2 mg/kg and 148.5 mg/kg MTX in a 6-h infusion, their beta half-lives for MTX were 2.6 and 2.0 h, while their gamma half-lives were 26.2 and 42.9 h, respectively. The 7OH-MTX beta half-lives were 5.8 and 4.0 h, and the gamma half-lives were 10.2 and 15.8 h. Plasma concentration ratios of 7OH-MTX to MTX were 28.5 and 18.1 at 24 h after MTX infusion. 7OH-MTX was detected in the 15-min sample after the beginning of the MTX infusion.
Binding, Competitive↗
Pharmacokinetics of cimetidine in critically ill children.
The pharmacokinetic behavior of cimetidine has not been described in children, and there is no authoritative guideline on cimetidine dosage for children. Cimetidine pharmacokinetics were studied after a single intravenous dose and during three, incremental rates of continuous infusion in critically ill children. The mean elimination half-life of cimetidine was 1.44 +/- 0.41 hours. Compared to adults, these children had a relatively faster clearance (14.21 +/- 2.85 ml/min/kg) of cimetidine and a larger apparent distribution volume (2.13 +/- 0.63 l/kg). Based on our results, it appears rational to initiate cimetidine at a daily dose of 24 mg/kg in critically ill children.
Age Factors↗
Theophylline. New thoughts about an old drug.
Explore the source record for details and available documents.
Asthma↗
Influence of specific gravity on intravenous drug delivery.
Explore the source record for details and available documents.
Humans↗
Ranitidine kinetics and dynamics. I. Oral dose studies.
Ranitidine, an H2-receptor antagonist, has been shown to reduce pentagastrin-stimulated gastric secretion. We examined the relationship between inhibition of gastric secretion and ranitidine serum concentration. Twelve normal male subjects received 20, 40, or 80 mg of ranitidine orally 90 min before starting a 3-hr continuous infusion of pentagastrin, 2 micrograms/kg/hr. Ranitidine, 20, 40, and 80 mg, reduced hydrogen ion output by 29%, 50%, and 70% and secretion volume by 21%, 37%, and 47%. Pepsin activity was reduced by 8%, 50%, and 49% by the same doses. Peak serum concentration was correlated positively with percent reduction in hydrogen ion output (r = 0.81, P less than 0.001) and volume (r = 0.71, P less than 0.01) over a 2-hr period. A 50% inhibition of hydrogen ion output was associated with a peak ranitidine serum concentration of 165 micrograms/l and subjects reached peak serum concentration 60 to 120 min after oral dosing. An appropriate therapeutic effect should be achieved with 8 hourly doses of 80 mg ranitidine. No clinically significant subjective or toxic biochemical effect of ranitidine was seen after single doses. White blood cell count was reduced in 11 of 12 subjects 7 days after ranitidine, an observation which calls for further investigation.
Administration, Oral↗
Ranitidine kinetics and dynamics. II. Intravenous dose studies and comparison with cimetidine.
Intravenous ranitidine has been shown to reduce pentagastrin-stimulated gastric secretion. Eight normal men received, in randomized order, 60 mg ranitidine or 300 mg cimetidine intravenously over 2 min. Both ranitidine and cimetidine induced decreases in volume hydrogen ion content and pepsin activity of stimulated gastric juice. Ranitidine half-life (t1/2) was 2.1 +/- 0.1 hr and cimetidine (t1/2) was 1.5 +/- 0.1 hr. Ranitidine volume of distribution was 1.6 +/- 0.1 l/kg and that of cimetidine was 1.12 +/- 0.12 l/kg. The clearance of ranitidine was 0.54 +/- 0.04 l/kg hr-1 and that of cimetidine was 0.5 +/- 0.05 l/kg hr-1. It is suggested that the intravenous loading dose of ranitidine necessary to attain a serum concentration of 200 micrograms/l (which would achieve a 50% inhibition of gastric acid) is 0.3 mg/kg, followed by an infusion rate of 0.11 mg/kg hr-1.
Adult↗
Acute and chronic drug abuse emergencies in Metropolitan Toronto.
From 3,548 drug overdose or abuse cases presenting at 21 Metropolitan Toronto hospitals' Emergency departments, data concerning demographic and medical characteristics, investigative and management procedures, drug analysis services, and disposition of patients were collected. Of the 3,548 cases, 2,723 (77%) were acute overdose and 816 (23%) were drug abuse. Drug overdose was more common than drug abuse for both sexes, but was more characteristic of females. The drugs most frequently alleged ingested were benzodiazepines (34%), ethanol (32%), salicylates (16%), and barbiturates (14%). The frequency with which particular classes of drugs are alleged in overdose corresponds closely to the frequency of prescribing these drugs in Ontario.
Adult↗
Analysis of pemoline in serum by high performance liquid chromatography: clinical application to optimize treatment of hyperactive children.
The analysis of pemoline (2-imino-5-phenyl-4-oxazolidine) by a rapid, sensitive, and specific high performance liquid chromatographic assay using ultraviolet detection is described. Only 100 microliters of plasma or serum is required. Analytical recoveries of 88% for pemoline and 93% for the internal standard (4-methylprimidone) are obtained by this procedure. Between-day precision studies of serum controls containing 10.2, 2.0, and 0.5 mg pemoline/liter produce coefficients of variation of 6.2, 9.4, and 16.2%, respectively. A clinical study of 28 children treated with pemoline demonstrated a linear relationship between drug dose and serum concentrations with an apparent therapeutic range falling between 1.7 and 7.0 mg/liter. These serum concentrations were achieved at drug dosages between 37.5 and 112.5 mg/day.
Adolescent↗
Propranolol and chlordiazepoxide effects on cardiac arrhythmias during alcohol withdrawal.
The pattern of cardiac arrhythmias and their treatment, by propranolol and chlordiazepoxide, during the first 48 hr of alcohol withdrawal has been studied. Prior to treatment, the incidence of serious and life-threatening arrhythmias was found to be very low and uncorrelated with most biochemical parameters. Propranolol treatment, while efficacious in controlling arrhythmias, was limited due to its association with hallucinations. Chlordiazepoxide was associated with poor early control of arrhythmias. The combination of propranolol and chlordiazepoxide was found to perform best overall with substantial reductions in arrhythmias and the fewest treatment failures.
Alcoholism↗
Alcohol use by patients admitted to hospital emergency rooms for treatment of drug overdose and misuse.
Persons admitted to hospital emergency rooms for treatment of drug misuse with concomitant alcohol use were generally found to be heavy drinkers.
Adolescent↗
Analysis of ranitidine in serum by high performance liquid chromatography.
We describe a simple and rapid micro method for the high pressure liquid chromatographic analysis of ranitidine, N-[2[[[5-[(dimethylamino)-methyl]-2-furanyl]methyl]thio]-ethyl-N'-methyl-2-nitro-1,1-ethenediamine in serum or plasma. The percentage analytical recovery of ranitidine and internal standard (metiamide) was 99% and 81%, respectively. The between-day precision of the procedure (n = 20) at ranitidine plasma concentrations of 500, 250, and 125 microgram/liter generated coefficients of variation of 6.2, 8.7, and 8.9%, respectively. The method was applied in preliminary studies to correlate serum concentrations of ranitidine with gastric acid secretion after continuous pentagastrin stimulation (2 microgram/kg/hr) in patients receiving an oral dose of 20, 40, or 80 mg of the drug.
Chromatography, High Pressure Liquid↗
A rapid high performance liquid chromatographic procedure for the analysis of cloxacillin and/or nafcillin in serum.
A rapid, reliable procedure for the analysis of cloxacillin and/or nafcillin in 100 microliter of serum or plasma is described. Percentage analytical recovery of cloxacillin, nafcillin, and internal standard (5-(p-hydroxyphenyl)-5-phenylhydantoin) were 94, 91, and 85%, respectively. The between-day precision of the method at cloxacillin concentrations of 2, 8, and 20 mg/liter was 14.7, 11.6, and 10.3%, respectively. At identical serum concentrations, the values obtained for nafcillin were 15.3, 12.4, and 12.2%, respectively. The method will be used to study the pharmacokinetics of both drugs in patients with cystic fibrosis who are on long-term therapy. Preliminary data providing the i.v. half-life, clearance, and volume of distribution are presented for two normal individuals.
Chromatography, High Pressure Liquid↗
Antihypertensive efficacy of propranolol given twice daily.
The therapeutic efficacy of propranolol in four and two daily doses was compared in 63 treated hypertensive patients in a multicentre trial. After 3 months of a stable diastolic blood pressure while receiving propranolol four times a day the patients were switched to a twice-a-day regimen, the drug being given at 8 am and 8 pm, with the same total daily dose, for 3 more months. Blood pressures and heart rates were measured at 8 am, 12 noon, 4 pm and 8 pm at 4-week intervals. There were no significant changes in mean blood pressure after the change to the twice-a-day regimen, although some patients reported new side effects. Compliance appeared to be unaffected.
Adolescent↗