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Biomedical subjects

D C Buss

Publications and source records attributed to D C Buss.

At least 19 recordsLinked to original sources
PubMed2004

Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine.

BACKGROUND: Transdermal nicotine is of value in active ulcerative colitis but causes adverse events because of systemic absorption. Nicotine enemas may give rise to fewer adverse events. AIM: To assess the pharmacokinetics of nicotine enemas in three doses. METHODS: Thirteen volunteers, all non-smokers but three ex-smokers, were given enemas on separate occasions containing 3, 6 and 9 mg of nicotine, in ascending dose order. Adverse events were recorded and blood samples taken over 8 h for measurement of serum nicotine and cotinine. RESULTS: Enemas were retained by most subjects. Eleven of 14 adverse events were 'early'--30-105 min after the enema, corresponding to maximum plasma nicotine concentrations; three events were later, 4-8 h after the enema and unrelated to the tmax. 'Early' adverse events occurred in eight subjects--six with 9 mg. The three highest plasma nicotine concentrations were with 9 mg and associated with headache, nausea and sweating. Only one had adverse events with 3 mg and withdrew from the study. Nicotine Cmax with 6 and 9 mg doses were respectively two and three times the value with 3 mg. Peak nicotine concentrations occurred 44-50 min after the enema. CONCLUSION: The 6 mg dose of nicotine probably represents the dose to use in clinical practice - for the highest therapeutic dose with a low risk of adverse events.

Adult↗
PubMed1999

ATP is involved in myocardial and vascular effects of exogenous bradykinin in ejecting guinea pig heart.

It has recently been reported that bradykinin induces selective left ventricular (LV) relaxation in isolated guinea pig hearts via the release of nitric oxide. Exogenous bradykinin also induces vasodilation, which is only partly due to nitric oxide release. In the present study we investigated the role of adenyl purines on these bradykinin-induced effects. Isolated ejecting guinea pig hearts were studied. LV pressure was monitored by a 2-Fr micromanometer-tipped catheter. ATP concentrations were measured using a luciferin-luciferase assay. Bradykinin (1 and 100 nM) caused a progressive acceleration of LV relaxation together with a transient increase in coronary flow. These effects were inhibited by the nonselective P(2) purinoceptor antagonist suramin (1 microM, n = 6) but were unaffected by the selective P(2x) purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (1 microM, n = 6). These myocardial and vascular effects of bradykinin were associated with increased ATP levels in coronary effluent. These data suggest that the selective enhancement of LV relaxation and rise in coronary flow induced by exogenous bradykinin involve endogenous ATP and the subsequent stimulation of P(2) purinoceptors.

Adenosine Triphosphate↗
PubMed1997

The effect of repeated-dose activated charcoal on the pharmacokinetics of sodium valproate in healthy volunteers.

AIMS: We investigated the effects of repeated-dose charcoal administered several hours after sodium valproate on the pharmacokinetics of a single dose of the drug in healthy volunteers. METHODS: The pharmacokinetics of sodium valproate were studied in seven healthy volunteers after administration of a syrup (300 mg) on two occasions, one of which was followed by administration of repeated doses of oral charcoal starting 4 h after the drug up to 32 h (total dose 80 g). RESULTS: Valproate was rapidly absorbed with maximum concentrations 1 h after administration. The area under the plasma concentration-time curve to 48 h (AUC (0.48 h)) was 408 +/- 114.5 (s.d.) mg l-1 h in the control phase and 398 +/- 108.6 mg l-1 h after charcoal and the t1/2 elimination was 20 +/- 6.8 h in the control phase, and 22 +/- 9.2 h after charcoal (NS). CONCLUSIONS: Repeated-dose activated charcoal does not appear to enhance the rate of elimination of sodium valproate after therapeutic doses of the drug and any beneficial effect of charcoal in overdose may be to prevent absorption of valproate still present in the gut.

Adult↗
PubMed1997

The effect of intravenous aminophylline on essential tremor.

AIMS: The effects of intravenous aminophylline (375 mg) or placebo (saline) were studied in 10 patients with benign essential tremor. METHODS: This was a single-blind crossover study. Patients received aminophylline by i.v. infusion over 15 min or saline at least 1 week apart. Tremor was measured by a peizoresistive accelerometer at 15 min intervals predose and up to 2 h. Plasma theophylline concentrations were measured by h.p.l.c. RESULTS: Tremor power was significantly greater following aminophylline (5.67-6.2 Hz) than placebo (5.6-5.9 Hz). CONCLUSIONS: We conclude that intravenous aminophylline potentiates benign essential tremor when given acutely by the intravenous route in the doses required to achieve therapeutic benefits in asthma.

Adolescent↗
PubMed1997

In vitro drug adsorption to charcoal, silicas, acrylate copolymer and silicone oil with charcoal and with acrylate copolymer.

1. The relative binding constants of four drugs to charcoal, silicone oil silicas and acrylate copolymers was studied using an in-vitro binding technique. 2. The maximum adsorption capacity (K2) was chosen as a measure of the degree of binding and calculated by fitting to the Langmuir equation. 3. Charcoal alone was shown to be the most effective of the adsorbents chosen. The possible use of silicone oils as an adsorbent delivery vehicle in treatment of overdose is discussed.

Acetaminophen↗
PubMed1993

A method for rapid determination of lorazepam by high-performance liquid chromatography.

A new sensitive method using solid-phase column extraction and high-performance liquid chromatography (HPLC) has been developed for the determination of lorazepam and its glucuronide metabolite in human plasma. Extraction was performed with a C2-Bond Elut column followed by reverse-phase HPLC of the sample. The detection limit of lorazepam in plasma was 0.5 micrograms/L. Standard curves over the concentration range from 2.5 to 75 micrograms/L had good linearity. Intra-assay variability ranged from 2.0 to 6.2% and interassay variability from 4.8 to 8% at the concentration range of 5-50 micrograms/L.

Chromatography, High Pressure Liquid↗
PubMed1990

Drug adsorption to charcoals and anionic binding resins.

1. The in-vitro binding of four drugs with differing physiochemical properties to two commercial charcoal preparations and two anionic binding resins was studied at 37 degrees C and pH 7.4. 2. The two charcoal preparations (Carbomix and Medicoal) behaved similarly and adsorbed metoclopramide and antipyrine to a greater degree than warfarin or paracetamol. 3. Cholestyramine had a significantly greater maximum adsorption capacity (K2) for warfarin and significantly lower adsorption capacity for paracetamol and metoclopramide than did the charcoals. 4. Colestipol behaved similarly but also bound metoclopramide to a significantly greater extent than did either cholestyramine or charcoal and antipyrine to a significantly lesser extent than did Carbomix. 5. There appeared to be no consistent relationship between the maximum adsorption capacity of the adsorbents for the drugs tested and the physicochemical properties of those drugs (e.g. basic or acidic structure, pKa or molecular weight).

Adsorption↗
PubMed1990

The effects of charcoal and sorbitol (alone and in combination) on plasma theophylline concentrations after a sustained-release formulation.

1. The effects of charcoal and sorbitol, alone and in combination, were investigated in eight healthy female volunteers who received 600 mg slow-release theophylline (two 300 mg capsules). 2. The area under the plasma concentration time curve to 24 h (AUC0-24) after theophylline alone was significantly greater than after both the charcoal and charcoal plus sorbitol phase. 3. Charcoal and charcoal with sorbitol also significantly reduced the maximum plasma theophylline concentration (Tmax) and time to maximum concentration (Cmax). 4. Sorbitol significantly increased Cmax and shortened Tmax. 5. Although sorbitol did not reduce the adsorptive efficacy of charcoal, its use alone may be deleterious in poisoning with sustained-release theophylline products.

Adult↗
PubMed1990

A rapid liquid chromatographic method for the determination of metoclopramide in human plasma.

A new sensitive analytical method is described for the measurement of metoclopramide in 1 ml plasma samples. The extraction step is followed by simple back-extraction and direct injection into the high-performance chromatographic (HPLC) column, with ultraviolet absorbance detection at 275 nm and reverse phase chromatography. The limit of detection for metoclopramide was 3 ng/ml and standard curves were linear over a concentration range of 5 to 1,000 ng/ml. The lowest quantifiable concentration of 5 ng/ml could be determined with a coefficient of variation of 6.5%. The method compares favourably with HPLC methods already described for metoclopramide and gives rapid and reproducible results in subjects receiving the drug.

Calibration↗
PubMed1989

The effect of theophylline on thyrotoxic tremor.

1. The effect of intravenous aminophylline on theophylline-induced tremor were studied in six hyperthyroid patients before and after treatment to euthyroidism. 2. Baseline tremor power was significantly greater in the hyperthyroid compared with the euthyroid state (P less than 0.05). 3. Aminophylline produced a significantly greater increase in tremor power in the hyperthyroid compared with euthyroid state. 4. There was a significant increase in plasma theophylline clearance and reduction in t1/2 elimination when patients were hyperthyroid but volume of distribution did not change. 5. Intravenous aminophylline potentiates the tremor produced in hyperthyroidism despite an increase in plasma theophylline clearance. A pharmacodynamic mechanism is therefore likely.

Aged↗
PubMed1989

Bioavailability of intranasal metoclopramide.

After intranasal administration of metoclopramide, (5 mg in 0.5 ml sterile water) the maximum plasma concentration of 13.5 +/- 7.3 (mean +/- s.d.) ng ml-1 was achieved. Absolute bioavailability was 50.5 +/- 29.5%, 110 +/- 41 min later. We conclude that the intranasal route does not allow rapid absorption of the drug and is not associated with greater bioavailability than the oral route.

Absorption↗
PubMed1987

Effect of aminophylline on the respiratory depressant action of intravenous adenosine in neonatal rabbits.

We administered intravenous adenosine to 11 neonatal rabbits. Adenosine depressed respiration in 10 of 11 rabbits. For the group as a whole the adenosine-induced respiratory depression was highly significant (p less than 0.001). After aminophylline administration to the same animals the respiratory effect of intravenous adenosine was abolished in 3 animals. In 7 animals the effect of adenosine was reversed and respiratory stimulation was observed. After aminophylline adenosine produced a significant (p less than 0.001) increase in respiration in the group studied. The alteration of responses to intravenous adenosine by aminophylline in neonatal rabbits is similar to the effect of aminophylline on respiratory responses to hypoxia in neonates. Such an effect of aminophylline and other methylxanthines on adenosine actions, possibly central in site may explain their beneficial effect in the treatment of apnoea in the human neonate.

Adenosine↗
PubMed1987

Determinants of free theophylline clearance in asthma.

1. The free and total plasma and saliva concentrations of theophylline were measured during a dosing interval at steady state in nineteen asthmatic subjects receiving a once-daily theophylline preparation (Riker TCR-1). 2. Saliva theophylline clearance (mean +/- s.d. 5.8 +/- 2.1l h-1) was closely related to total plasma theophylline clearance (mean 3.6 +/- 1.2l h-1) (r = 0.958, n = 19, P less than 0.001). 3. Saliva theophylline clearance was closely related (r = 0.967, n = 19, P less than 0.001) and numerically very similar to the free plasma theophylline clearance (mean 5.8 +/- 1.9l h-1) (mean difference = 0.06 +/- 0.12 s.e. mean). 4. Free plasma theophylline clearance was significantly, although weakly, related to body weight and to the plasma free thyroxine concentration which together accounted for over 40 per cent of the variability in free clearance. 5. Theophylline administered for 2 weeks did not affect plasma free thyroxine (FT4) free tri-iodothyronine (FT3) or reverse tri-iodothyronine (rT3) concentrations compared with placebo.

Adult↗
PubMed1987

The effect of charcoal on mefenamic acid elimination.

Mefenamic acid suppository 500 mg was administered by rectum to eight healthy adult volunteers followed by either activated charcoal 5 g orally at hourly intervals for 7 h or an equal volume of water on two separate occasions 7 days apart. Administration of charcoal did not significantly affect the pharmacokinetic variables of mefenamic acid. Thus the beneficial effects of charcoal in the treatment of mefenamic acid overdose are largely due to interference with absorption, rather than enhancement of elimination of the drug.

Adult↗
PubMed1986

Comparison of respiratory effects of intravenous adenosine in neonatal and adult rabbits.

We administered adenosine by repeated intravenous bolus doses to 34 neonatal rabbits in a dose of 120 micrograms X kg-1 (which we had previously found to stimulate respiration in adult rabbits). In 13 neonatal animals adenosine produced transient respiratory depression. In 15 neonatal animals the change in respiration in response to adenosine did not reach statistical significance. In two animals a transient increase in respiration occurred in response to adenosine. In the neonatal group as a whole intravenous adenosine significantly depressed ventilation. In eleven of the animals studied as neonates, respiratory responses to adenosine were again studied in adulthood. In 10 animals respiratory stimulation occurred in response to adenosine. In the adult group adenosine significantly increased ventilation, in contrast to its effects in the neonatal group. The respiratory effects of intravenous adenosine have not been previously described in neonatal animals. Respiratory stimulation produced by intravenous adenosine in adult rabbits contrasts with the respiratory depression commonly seen in neonatal rabbits in this study. It is suggested that altered responses to adenosine may be involved in the difference between the ventilatory response to hypoxia in adult and neonatal animals.

Adenosine↗
PubMed1986

The disposition of theophylline in blood in chronic obstructive lung disease.

In 42 subjects with chronic obstructive lung disease receiving chronic oral theophylline therapy, the venous whole blood theophylline concentration was closely related to the total plasma theophylline concentrations (r = 0.976, p less than 0.001). The blood/plasma concentration ratio was 0.85 +/- 0.13 and was not related to the haematocrit or the free fraction of theophylline in plasma. The red blood cell theophylline concentration was closely related and numerically similar to the free plasma concentration. This indicates that the free plasma concentration is the most important determinant of red blood cell concentration, and that binding of drug by red blood cells or active uptake into erythrocytes is unlikely to occur. Whole blood concentration can be used to predict plasma theophylline concentration in subjects with obstructive lung disease in situations where preparation of plasma is inconvenient. The therapeutic range for whole blood concentration is approximately 8.5-17 mg/L.

Adolescent↗
PubMed1986

The plasma protein binding of metoclopramide in health and renal disease.

The plasma protein binding of metoclopramide was measured after addition of the drug (60 ng ml-1) to plasma from 18 patients with renal disease and 18 age and sex matched healthy individuals. The mean free fraction in renal disease (0.59 range 0.41-0.71) was not significantly different from controls (mean 0.6 range 0.56-0.69). In both groups the binding ratio of metoclopramide was significantly related to plasma alpha 1-acid glycoprotein (AAG) concentration but not to albumin or plasma non-esterified fatty acids concentration. Metoclopramide bound to human serum albumin (HSA) to a limited extent and to human AAG to a greater extent indicating that AAG is the major binding protein for the drug in plasma.

Blood Proteins↗