Three control animals similarly received a 6 h infusion of vehicle only. The infusion rates were 0.3–0.4, 0.6–0.8, and 1.2–1.6 mL/h in the 250, 500, and 1,000 mg/kg dose groups, respectively. The number of animals in each treatment group was as follows: 4, 6, and 25 animals received P188-P in the 250, 500, and 1,000 mg/kg dose groups, respectively, and 3, 10, and 30 animals received P188-NF in the 250, 500, and 1,000 mg/kg dose groups,

respectively. Serum samples for creatinine testing were collected at 3 h (i.e., during the infusion), at 6 h (i.e., at the end of the infusion) and at 24 and 48 h following the end of the infusion (post-infusion). Creatinine levels were measured according to Heinegård and Tiderström [35]. At 48 h post-infusion, the animals were humanely euthanized and their kidneys were harvested and processed for histopathologic examination. The reversibility of treatment-induced see more changes was examined in a separate group of remnant-kidney rats following a 6-h infusion of either P188-P (1,000 mg/kg/h) or P188-NF (1,000 mg/kg/h), with histopathology examination conducted at 24, 48, and 144 h post-infusion. 2.4 Histopathology Tissue sections of the remnant kidneys were prepared according to standard LY3023414 ic50 techniques and stained with hematoxylin and eosin (H&E) and with periodic acid–Schiff (PAS). Light

microscopic examinations were performed by a renal pathologist blinded to treatment. Tissues were also examined by transmission electron microscopy for treatment-induced ultrastructural effects. 2.5 Clinical Studies Two clinical studies were conducted to evaluate the effects of P188-P on safety

and renal function in patients with SCD. Both studies Gemcitabine mouse involved test agent administration consisting of a loading dose administered intravenously over 1 h, followed by a maintenance dose administered over either 23 or 47 h. In one study (study C97-1248), 126 subjects were treated with a total dose of 1.5 g/kg. In the other study (study C97-1243), 42 subjects were randomized in an escalating manner to receive total doses ranging from 1.1 to 2.9 g/kg. Urinary and plasma-based renal function biomarkers were evaluated Methisazone at baseline and throughout the C97-1243 trial, and plasma creatinine was assessed in both trials. All studies were conducted according to Good Clinical Practice (GCP)/International Conference on Harmonisation (ICH) standards on consented subjects, and specimens were collected accordingly. 3 Results 3.1 Purification of P188-NF Representative GPC profiles of P188-NF and P188-P are shown in Fig. 2. The predominant peak (between 14 and 15 minutes) identifies the desired molecular species. P188-NF typically contains about 5 % (by weight) LMW substances (<5,500 Da) [see Fig. 2a; dashed-line circle eluting after 15 min], which were targeted for removal. These LMW substances are greatly reduced or absent in P188-P [see Fig. 2b, dashed-line circle].