Pharmacokinetics of ampicillin and its prodrugs bacampicillin and pivampicillin in man

Five healthy fasting male subjects were each given single doses of intravenous ampicillin (471 mg), oral ampicillin tablets (495 mg), oral bacampicillin hydrochloride tablets (562 mg ampicillin equivalent), and oral pivampicillin hydrochloride capsules (491 mg ampicillin equivalent) in a crossover experiment. The resulting concentrations of ampicillin were determined in plasma and urine. The pharmacokinetic analysis was made according to a two-compartment open model. The total distribution volume of unbound ampicillin during the disposition phase was 0.247 ± 0.045 (sd) liter/kg, which is only slightly more than the extracellular fluid, suggesting that tissue binding and intracellular distribution of ampicillin are limited. The bioavailability of the esters bacampicillin (86 ± 11%) and pivampicillin (92± 18%) was significantly greater than that of ampicillin (62 ± 17%); however, the difference between the esters was not statistically significant. The absorption for all drugs given orally proceeded at a constant rate, suggesting zero-order release rates from the products. The absorption rate was highest for bacampicillin (0.89 ± 0.39% of dose absorbed per minute), followed by pivampicillin (0.64 ± 0.19) and ampicillin (0.58 ± 0.16). Bacampicillin also had the shortest lag time for the start of absorption (7.0 ± 0.9 min) under the present conditions. Thus, in comparison with ampicillin, the esters have a higher bioavailability, which, in fact, is close to the theoretically highest possible value by clearance concepts. The higher bioavailability in connection with higher absorption rates may be clinically important in ampicillin treatment by the oral route.This work was supported by the Swedish Medical Research Council, Project No. 522 (L. O. B.).     

Risk factors for anal sphincter tears: the importance of maternal position at birth

Objective  To assess the role of birth position in the occurrence of anal sphincter tears (AST).
Design  Observational cohort study.
Setting  South Hospital in Stockholm, a teaching hospital with around 5700 births per year.
Population  Among all 19 151 women who gave birth at the South Hospital during the study period 2002–05, 12 782 women met the inclusion criteria of noninstrumental, vaginal deliveries.
Methods  Data on birth position and other obstetric factors were analysed in relation to occurrence of AST.
Main outcome measure  Third- and fourth-degree AST.
Results  AST occurred in 449 women (3.5%). The trauma was more frequent in primiparous (5.8%) than in multiparous women (1.7%). The highest proportion of AST was found among women who gave birth in lithotomy position (6.9%), followed by squatting position (6.4%). Logistic regression analyses showed that lithotomy (adjusted OR 2.02, 95% CI 1.58–2.59) and squatting positions (adjusted OR 2.05, 95% CI 1.09–3.82) were associated with a significantly increased risk for AST. Other major risk factors for anal sphincter trauma were primiparity (adjusted OR 3.29, 95% CI 2.55–4.25), prolonged second stage of labour >1 hour (adjusted OR 1.52, 95% CI 1.11–2.10), infant birthweight more than 4 kg (adjusted OR 2.12, 95% CI 1.64–2.72) and large infant head circumference (adjusted OR 1.57, 95% CI 1.23–1.99).
Conclusion  Lithotomy and squatting position at birth were associated with an increased risk for AST also after control for other risk factors.     

On the mechanisms of glutathione depletion in hepatocytes exposed to morphine and ethylmorphine

Incubation of isolated rat hepatocytes with either morphine or ethylmorphine resulted in glutathione (GSH) depletion followed by loss of cell viability. Pretreatment of cells with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inactivate glutathione reductase did not markedly affect the rates of GSH depletion seen in untreated cells. In contrast, hexobarbital stimulated H2O2 production in isolated liver microsomes, incubated aerobically with NADPH, whereas the effects of morphine and ethylmorphine on microsomal H2O2 production were minimal. Finally, incubation of hepatocytes with radioactively labeled morphine resulted in formation of 2 glutathione conjugates, one of which was tentatively identified as formyl glutathione. We conclude that GSH consumption during the metabolism of morphine or ethylmorphine by hepatocytes is due mainly to formation of glutathione conjugates.     

First imaging results of an intraindividual comparison of 11C-acetate and 18F-fluorocholine PET/CT in patients with prostate cancer at early biochemical first or second relapse after prostatectomy or radiotherapy

Purpose

¹⁸F-Fluorocholine (FCH) and ¹¹C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers.

Methods

The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤5 ng/ml) or RP and salvage RT (9 patients, PSA ≤5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307?±?16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994?±?72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results.

Results

PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen’s kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later.

Conclusion

Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging.     

Factor Structure of the Urdu Version of the Spence Children's Anxiety Scale in Pakistan

Spence Children's Anxiety Scale (SCAS) is one of the most commonly used self-report questionnaires to measure symptoms of anxiety disorders in adolescents. Despite its common use, studies that examine the psychometric properties of SCAS in Pakistan is lacking. Therefore, the purpose of this study was to examine the psychometric properties of the Urdu translated version of the SCAS among adolescents in Pakistan. A total of 1277 students (708 boys and 569 girls), aged 13 to17 years, who had been recruited from 13 schools in Rawalpindi, Pakistan participated in the study. The mean overall anxiety score was significantly higher in girls than males on all the SCAS subscales except for obsessive compulsive disorder. The internal consistency of the Urdu SCAS was good. Confirmatory factor analyses supported six separate factor structures. Results of the study are discussed with reference to the sociocultural milieu of Pakistan and culture sensitive conceptualization of anxiety and its subtypes.