Saliva versus Plasma Relative Bioavailability of Tolterodine in Humans: Validation of Class III Drugs of the Salivary Excretion Classification System.

Relative bioavailability study of tolterodine in healthy human volunteers was done using saliva and plasma matrices in order to investigate the robustness of using saliva instead of plasma as a surrogate for bioavailability and bioequivalence of class III drugs according to the salivary excretion classification system (SECS). Saliva and plasma samples were collected up to 16 h after 2 mg oral dose. Saliva and plasma pharmacokinetic parameters were calculated by non compartmental analysis using Kinetica program V5. Human effective intestinal permeability was optimized by SimCYP program V13. Tolterodine falls into class III (High permeability/Low fraction unbound to plasma proteins) and hence was subjected to salivary excretion. A high pearsons correlation coefficient of 0.97 between mean saliva and plasma concentrations, and saliva/plasma concentrations ratio of 0.33 were observed. In addition, correlation coefficients and saliva/plasma ratios of area under curve and maximum concentration were 0.98, 0.95 and 0.42, 0.34 respectively. On the other hand, time to reach maximum concentration was higher in saliva by 2.37 fold. In addition, inter subject variability values in saliva were slightly higher than plasma leading to need for slightly higher number of subjects to be used in saliva studies (55 vs. 48 subjects). Non-invasive saliva sampling instead of invasive plasma sampling method can be used as a surrogate for bioavailability and bioequivalence of SECS class I drugs when adequate sample size is used.

[Intra-uterine fetal death by knife: case report]. / Mort foetale intra-utérine par arme blanche (à propos d'un cas).

INTRODUCTION: Opened injuries by knife are rare in pregnant women and are responsible of foetal death in most cases. OBSERVATION AND COMMENTARY: We report a case of a 27-years woman, in her 8th months of pregnancy, victim of three knife punchs in her right iliac fossa. An emmergent laparotomy revealed deep wounds in the uterus and its right vascular pedicles, and a right external iliac artery lesion. Hysterectomy was performed and the extracted fetus was dead. He had two wounds in skull and back. Foetal death is common in opened knife injuries especially at the end of pregnancy. On one hand, the fetus has an abdominal situation that expose him to penetrating lesions. On the other hand, the uterus is richly vascularized during this period of pregnancy, thus any uterine or pedicular wound could result in a maternal hemorrhagic shock and hence a poor foetal and maternal prognosis. CONCLUSION: Knife injuries in pregnant women could compromise the foetal prognosis. Managmanent should be early and requires a close collaboration between resuscitators, obstetricians and vascular surgeons.