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C D Bevan

Publications and source records attributed to C D Bevan.

10 recordsLinked to original sources
PubMed2000

A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates.

The determination of aqueous solubility in a high-throughput screening environment is invaluable in the selection of the most promising potential drug candidates. We describe a fast method based on laser nephelometry that can determine the solubility of potential drug candidates (usually from combinatorial chemistry) supplied as dimethyl sulfoxide (DMSO) solutions in 96-well plates. In the sample, the percent DMSO is kept constant allowing direct comparison of results. The nephelometric method has been shown to produce results equivalent to those produced by an HPLC method and to be largely unaffected by colored solutions.

Chromatography, High Pressure Liquid↗
PubMed2000

Rapid-gradient HPLC method for measuring drug interactions with immobilized artificial membrane: comparison with other lipophilicity measures.

A fast-gradient high-performance liquid chromatographic (HPLC) method has been suggested to characterize the interactions of drugs with an immobilized artificial membrane (IAM). With a set of standards, the gradient retention times can be converted to Chromatographic Hydrophobicity Index values referring to IAM chromatography (CHI(IAM)) that approximates an acetonitrile concentration with which the equal distribution of compound can be achieved between the mobile phase and IAM. The CHI(IAM) values are more suitable for interlaboratory comparison and for high throughput screening of new molecular entities than the log k(IAM) values (isocratic retention factor on IAM). The fast-gradient method has been validated against the isocratic log k(IAM) values using the linear free energy relationship solvation equations based on the data from 48 compounds. The compound set was selected to provide a wide range and the least cross-correlation between the molecular descriptors in the solvation equation: (2) where SP is a solute property (e.g., logarithm of partition coefficients, reversed-phase (RP)-HPLC retention parameters, such as log k, log k(w), etc.) and the explanatory variables are solute descriptors as follows: R(2) is an excess molar refraction that can be obtained from the measured refractive index of a compound, pi(2)(H) is the solute dipolarity/polarizability, summation operatoralpha(2)(H) and summation operatorbeta(2)(0) are the solute overall or effective hydrogen-bond acidity and basicity, respectively, and V(x) is the McGowan characteristic volume (in cm(3)/100 mol) that can be calculated for any solute simply from molecular structure using a table of atomic constants. It was found that the relative constants of the solvation equation were very similar for the CHI(IAM) and for the log k(IAM). The IAM lipophilicity scale was quite similar to the octanol/water lipophilicity scale for neutral compounds. The effect of charge on the interaction with IAM was studied by varying the mobile phase pH.

Chromatography, High Pressure Liquid↗
PubMed1995

Clinical, laparoscopic and microbiological findings in acute salpingitis: report on a United Kingdom cohort.

OBJECTIVE: To determine the clinical features and microbial aetiology of acute salpingitis in women attending an inner city teaching hospital. DESIGN: Prospective, longitudinal cohort study. SUBJECTS: One hundred and forty-seven women presenting consecutively with acute abdominal pain and clinical signs of acute salpingitis were evaluated microbiologically and laparoscopically. RESULTS: One hundred and four women (70.7%) had acute salpingitis diagnosed at laparoscopy. Other pathological conditions were identified in 20 women (13.6%). No visually identifiable pathology was found in 23 (15.6%). Thirty-five women with acute salpingitis had evidence of pelvic adhesions (33.7%). Bilateral tubal occlusion was present in 6 (5.8%) cases. Chlamydia trachomatis was identified in the genital tract in 40 (38.5%) of the women with acute salpingitis and Neisseria gonorrhoeae in 15 (14.4%). A dual infection was present in eight cases (7.7%). Serological evidence suggested that a further seven women (6.7%) had acute chlamydial infections at the time of diagnosis. C. trachomatis was identified in the genital tract of 5/23 (21.7%) of the women who had no laparoscopic evidence of intra-abdominal pathology. CONCLUSIONS: The responsible care of women with suspected acute salpingitis depends on establishing an accurate diagnosis, so that appropriate therapy can be instigated. This study provides evidence to challenge the outpatient management of acute salpingitis on clinical grounds alone as potentially inadequate. Early laparoscopy in hospitalised women improves diagnostic precision and accurately determines disease severity, providing prognostic information for future fertility. In this urban population, sexually transmitted micro-organisms were the commonest pathogens found in the genital tract of women with acute salpingitis. The high prevalence of C. trachomatis in these women suggests that appropriate chemotherapy for acute salpingitis should always include a specific antichlamydial agent.

Acute Disease↗
PubMed1987

Pharmacokinetics of loprazolam and its principal metabolite in young subjects and elderly hospital patients.

1. The pharmacokinetics of loprazolam and its principal pharmacologically active metabolite, the piperazine N-oxide, were compared in young subjects (aged 21-25 years) and elderly patients (aged 63-86 years) following single oral evening doses (0.5 mg and 1 mg). 2. Plasma loprazolam was assayed by a specific h.p.l.c./g.c. method. The N-oxide metabolite was assayed by gas chromography. 3. Mean times to peak plasma concentration of loprazolam did not differ significantly between young and elderly subjects and ranged from 1.6-2.7 h. There was, however, a longer mean time to peak concentration of the N-oxide metabolite in the elderly but this was only statistically different after the 0.5 mg dose (4.5 mg young, 6.4 h elderly). 4. Mean peak plasma concentrations of loprazolam did not differ significantly between young and elderly nor did plasma concentrations of the N-oxide metabolite. 5. Although the mean elimination half-life of loprazolam was not statistically significantly different between young and elderly subjects (range 10.9-16.0 h) there was a trend towards somewhat longer half-lives in the elderly. Furthermore, there was a small but significant increase in the half-life of the N-oxide metabolite in the elderly after the 1 mg dose from 11.7 h to 16.7 h. 6. The areas under the plasma concentration time curves for both loprazolam and its N-oxide were greater in the elderly being some 50-68% (mean 132.0 and 111.5 ng/ml h) above those found in young subjects (mean 89.8 and 66.0 ng/ml h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Correlation of the clinical pharmacodynamics of loprazolam with serum concentration.

Six healthy fasted volunteers each received oral doses of a placebo, 1 mg and 2 mg loprazolam with one week between treatments using a double-blind balanced crossover design. Serum samples were obtained at selected times after dosing for measurement of loprazolam using a combined high-performance liquid and gas chromatographic assay. Drug effect was also measured at the corresponding times using self-assessment scales and psychomotor tests. The serum levels of loprazolam followed a somewhat irregular shape with secondary and tertiary peaks possibly associated with food intake. The maximum serum levels of loprazolam following 1 mg and 2 mg doses of the drug (6.0 +/- 2.6 and 11.3 +/- 2.9 ng/ml, respectively) occurred at approximately one hour after dosing. Both the maximum serum levels and the area under the curve of loprazolam measured to six hours increased in direct proportion to dose. Statistically significant drug effects were seen after 2 mg loprazolam, although the subjects also appeared sedated after 1 mg doses. There appeared to be a good correlation between the logarithm of the serum concentration of loprazolam and effect which suggested that the hypnotic activity of the drug was not mediated via a long-lived metabolite. A threshold serum concentration associated with evident sedation was observed at approximately 3 ng/ml.

Adult↗
PubMed1983

Single and repeated dose kinetics of the hypnotic agent loprazolam in healthy volunteers.

The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after the first and eighth dose. Maximum levels of approximately 10 ng ml-1 (range 3.6 to 15.5 ng ml-1) were reached within about 2.5 h after dosing. The post-peak levels declined in a single exponential fashion with an overall mean +/- SD half-life of 7.06 +/- 1.98 h and total areas under the curve ranging from 35.9 to 189.0 ng ml-1 h. There were no statistical differences between the values for the first and eighth doses. There was no evidence to suggest that significant accumulation of parent drug or receptor active benzodiazepine-type materials had occurred, and it is concluded that the kinetics of loprazolam would allow repeated daily doses of 2 mg.

Adult↗
PubMed1983

Metabolism of loprazolam in rat, dog and man in vivo.

The metabolism of 14C-loprazolam has been studied in rat, dog and man in vivo. In rat, the major metabolic pathways were hydroxylation on the benzodiazepine ring, and reduction and acetylation of the nitro group. Both metabolites were identified by co-chromatography with standards, and were present in urine and bile conjugated with glucuronic acid. In both dog and human urine and bile significant amounts of the piperazine-N-oxide were found. This N-oxide was identified by co-chromatography with authentic compound and by mass spectroscopy. Both loprazolam and the dog biliary metabolites were hydrolysed spontaneously to polar material. Neither treatment with beta-glucuronidase nor incubation with gut microflora had any further effect. Only polar metabolites were found in dog and human faeces. The principal non-polar material found in rat plasma was the diazepine-hydroxy compound, and little loprazolam was present. Significant levels of loprazolam and lower levels of an unidentified metabolite were found in ether extracts of dog and human plasma. Both the piperazine-N-oxide and loprazolam were found in similar quantities in chloroform extracts of human plasma, and at two hours after dosage, the N-oxide and loprazolam accounted for greater than 90% of the radioactivity present in the plasma.

Animals↗
PubMedDate not supplied

Efficacy and safety of azithromycin as monotherapy or combined with metronidazole compared with two standard multidrug regimens for the treatment of acute pelvic inflammatory disease.

The objective of the study was to compare the efficacy of azithromycin, alone or with metronidazole, versus two standard multidrug regimens for the treatment of acute pelvic inflammatory disease (PID). Patients with PID were treated with once-daily intravenous (i.v.) azithromycin 500 mg for 1 day or 2 days followed by once-daily azithromycin 250 mg orally for a total of 7 days, alone or with three-times-daily metronidazole 400 mg or 500 mg i.v. then orally for a total of 12-14 days. The comparators were either metronidazole + doxycycline + cefoxitin + probenecid or doxycycline + amoxycillin/clavulanate given at standard recommended doses for up to 21 days. In total, 309 patients were treated for PID. The diagnosis was confirmed laparoscopically in 74.8% of patients. Rates of clinical success for azithromycin, alone (97.1%) or with metronidazole (98.1%), were comparable to those for the comparator regimens (94.6%). Eradication rates for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma hominis and anaerobes were also comparable for each of the treatment groups. Both azithromycin regimens were well tolerated. In conclusion, azithromycin, alone or with metronidazole, provides a shorter, simpler treatment option for the successful management of acute PID.

Acute Disease↗