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Biomedical subjects

J Moncrieff

Publications and source records attributed to J Moncrieff.

61 records · Page 4Linked to original sources

Pharmacokinetics of ceftazidime in premature, newborn and young infants.

The pharmacokinetics of ceftazidime, a new injectable broad-spectrum cephalosporin with high anti-pseudomonal activity, were studied in 50 preterm, full-term and young infants after an intravenous bolus dose of 30 mg/kg. The serum concentrations of ceftazidime were higher in the younger babies, both premature and full-term. In infants over 2 months of age blood levels were similar to those of adult volunteer subjects. No untoward effects were encountered. Considering the in vitro activity of ceftazidime against a wide spectrum of pathogenic bacteria, the present dose schedules, 25-50 mg/kg/d for babies less than 2 months of age and 50-100 mg/kg/d for those 2-12 months of age, appear to be appropriate. Until more experience is gained with ceftazidime in neonates, monitoring of trough levels to ensure adequate blood concentrations would be ideal.

Age Factors↗

Influence of food and reduced gastric acidity on the bioavailability of bacampicillin and cefuroxime axetil.

The present study was designed to investigate the effect of food and of a raised intragastric pH on the bioavailability of two prodrug beta-lactam, antibiotics, namely bacampicillin and cefuroxime axetil. Six healthy volunteers participated in an intraindividual comparison of absorption of (a) prodrug, (b) breakfast, followed by prodrug, (c) breakfast, ranitidine and sodium bicarbonate followed by prodrug, and (d) ranitidine and sodium bicarbonate, followed by prodrug. All volunteers were dosed with both bacampicillin and cefuroxime axetil under the above regimens. The drug-free periods between trials were 7 days. Blood samples were obtained before and 20, 40, 60, 90, 120, 150, 180, 210 min and 4, 5, 6, 8 and 10 h after administration. The urine was collected for a period of 10 h after dosing with the antibiotic. An estimation of the relative bioavailability of the drugs under the various regimens was made by comparing the average areas under the serum concentration time curves and also the amounts recovered in the urine. Both food and reduced gastric acidity decreased the bioavailability of bacampicillin (as ampicillin) and these variables had an additive lowering effect on the AUC and percentage urinary recovery. Possibly this ester becomes partially hydrolyzed prior to absorption on raising the intragastric pH. Adsorption onto food components or complexing with proteins may also play a role in the reduced bioavailability of bacampicillin in the presence of food. In contrast, the absorption of the cefuroxime ester was enhanced postprandially. This may be rationalized in terms of delayed gastric emptying and gastrointestinal transit which allows more complete dissolution or prolonged residence at the most favourable site of absorption in the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A preliminary pharmacokinetic study of ceftazidime in premature, new born and small infants.

Fifty neonates and infants with suspected or proven bacterial infection were given 30 mg/kg of ceftazidime as a single intravenous dose to investigate the pharmacokinetics of ceftazidime. The mean serum half-lives for babies aged less than 2 months was 4.18 +/- 1.60 h and for those aged 2 to 12 months 2.00 +/- 0.64 h. Dose bands of 25 to 50 mg/kg/day for those less than two months and 50-100 mg/kg/day for those aged 2 to 12 months are recommended for the treatment of suitable bacterial infections.

Bacterial Infections↗

Sexual abuse and the subsequent development of alcohol problems.

The literature on sexual abuse and alcohol problems has been reviewed. Various methodological issues are relevant in determining whether there is merely an association or also a causal relationship. These include the definition of sexual abuse, the degree and timing of abuse, the methods of data collection, sample selection, the presence or absence of control groups, possible recall bias, difficulties with prospective studies for this subject, and the definition of alcohol misuse or dependence. Results with community and victim samples are conflicting, but studies on samples of problem drinkers suggest an association between severe alcohol problems and previous sexual abuse, at least in women. The association may be especially strong for earlier and more severe forms of sexual abuse. Possible mechanisms for an association were examined and are: (1) sexual abuse as a cause of alcohol misuse; (2) alcohol misuse predisposing people to sexual assault; (3) sexual assault and alcohol misuse both resulting from another factor; (4) sexual abuse predisposing to other conditions associated with alcohol misuse; and (5) an artefactual association. Regardless of the role of sexual abuse in causing alcohol problems, the available evidence suggests that victims of sexual abuse may present to services with more problematical patterns of drinking and more concurrent psychiatric disorder.

Alcoholism↗

A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse.

The opioid antagonist, naltrexone, is reported, in single centre studies, to improve the clinical outcome of individuals with alcohol dependence participating in outpatient psychosocial programmes. This is the first multicentre controlled study to evaluate the efficacy and safety of naltrexone as adjunctive treatment for alcohol dependence or abuse. Patients who met criteria for alcohol dependence (n = 169) or alcohol abuse (n = 6) were randomly assigned to receive double-blind oral naltrexone 50 mg daily (n = 90) or placebo (n = 85) for 12 weeks as an adjunct to psychosocial treatment. The primary efficacy variable was time to first episode of heavy drinking; secondary efficacy assessments included time to first drink, alcohol consumption, craving, and changes in the serum biological markers gamma-glutamyl transferase (GGT), and aspartate and alanine aminotransferases. Compliance was assessed by tablet counts and, in the naltrexone-treated group, by measurement of urinary concentrations of 6-ss-naltrexol. Forty-nine (58%) patients randomized to placebo and 53 (59%) randomized to naltrexone did not complete the study. In intention-to-treat analyses, there was no difference between groups on measures of drinking. The median reduction from baseline of serum GGT (P: < 0.05) and the reductions in alcohol craving (Obsessive and Compulsive Drinking Scale: OCDS) were greater in the naltrexone group (P: < 0.05), from approximately half-way through the study. Of 70 patients (35 placebo; 35 naltrexone) who met an a priori definition of compliance (80% tablet consumption, attendance at all follow-up appointments), those allocated to naltrexone reported consuming half the amount of alcohol (P: < 0.05), had greater median reduction in serum GGT activity (P: < 0.05), and greater reduction in alcohol craving (OCDS total score: P: < 0.05; Obsessive subscale score: P: < 0.05), compared to patients in the placebo group. Use of naltrexone raised no safety concerns. Naltrexone is effective in treating alcohol dependence/abuse in conjunction with psychosocial therapy, in patients who comply with treatment.

Adult↗

A foreshortened method of measuring liquid gastric emptying in normal volunteers.

The purpose of this study was to compare the cumulative fraction absorbed-time profile method of paracetamol with the shorter proportional area under the curve method of paracetamol by pretreating normal volunteers with cisapride, codeine and metoclopramide with and without neostigmine. Both methods are sensitive and comparable in defining early phase liquid gastric emptying, with the proportional area under the curve method having the advantage of providing the relevant information with a two-hour study period.

Acetaminophen↗