This was performed by non-linear regression with global fitting of the rate constant in a monoexponential decay model (Ct = Ci × exp(−k · t)). Here, Ci is the initial concentration and Ct is the concentration after time t when elimination occurs with a rate constant of k. In this analysis, Ct and Ci were allowed to vary between individuals to account for differences in exposure. Patients in whom the concentrations were not greater than the LOR in at least two samples were excluded Lumacaftor concentration from the kinetic analysis. All regressions were conducted using GraphPad Prism version 4.03 for Windows, GraphPad Software, San Diego CA USA, www.graphpad.com. Serial samples were obtained in 33
patients and in 25 of these the concentrations were greater than the limit of reporting (5 mg/L) allowing inclusion in the analyses. All patients presented following acute intentional self poisoning and there was only one death. In the case of the survivors, regardless of the initial MCPA concentration, all survivors demonstrated signs of mild poisoning (predominantly nausea, vomiting and/or mild abdominal pain) and were discharged from hospital within 24–48 h (Table 1). The clinical sequelae of
the patient who died have been reported previously (patient 7 in Table 2 (Roberts et al., 2005)). Briefly, this was a 45-year-old man with an altered level of consciousness who developed progressive tachycardia, tachypnoea, fever, haematuria and died 10 h post-admission to hospital.
His treatment included intravenous fluids, endotracheal intubation and a single dose of sodium bicarbonate 25 mmol. For all patients except three, the Dolutegravir price time of the maximum plasma concentration (Tmax) buy Rucaparib was noted on admission (Table 1). In the others the Tmax was at 3.7 h for two patients and 7 h post-ingestion in the third patient. This suggests that the absorption phase can be prolonged. The concentration–time profiles for 6 patients with the highest number of samples are shown in Fig. 2. The initial rapid decrease in MCPA concentration in A4505 and A4546 possibly represents a distribution phase. An inflection in the semi-logarithmic concentration–time profile is observed in A162 and A225 producing a biphasic convex (downward-concave) curve (similar to that noted in rat administered high doses (Roberts and Buckley, 2007a)). A biphasic convex elimination curve was not obvious in the other patients, which may reflect the infrequent and short duration of sampling. In general, the free concentration mirrored the total concentration suggesting rapid equilibration between free and bound MCPA. Both curves are approximately log-linear which may suggest first-order elimination in this concentration range, however due to the limited frequency of sampling, zero order elimination cannot be excluded. The plasma concentration–time profile for the patient who died is shown in Fig. 3. It differed substantially to that of other patients shown in Fig. 2.