Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors.

Purpose: To develop a population pharmacokinetics (PPK) model for rucaparib, an oral poly(ADP-ribose) polymerase inhibitor.

Methods: The PPK analysis used PK data from patients in Study 1014 (NCT01009190, n = 35), Study 10 (NCT01482715, n = 123), and ARIEL2 (NCT01891344, n = 300), including intensive intravenous data (12-40 mg), intensive and sparse oral data (12-360 mg single-dose, 40-500 mg once daily, and 240-840 mg twice daily [BID]), and intensive single-dose oral data under fasted conditions and after a high-fat meal (40, 300, and 600 mg).

Results: Rucaparib PK was well described by a two-compartment model with sequential zero-order release and first-order absorption and first-order elimination.

Population pharmacokinetic modeling and simulations of berotralstat for prophylactic treatment of attacks of hereditary angioedema.

Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by recurrent episodes of swelling of the skin, larynx, gastrointestinal tract, genitals, and extremities that can be disruptive to patient quality of life. Dysregulation of plasma kallikrein activity leads to increased production and accumulation of bradykinin in HAE and causes attacks of angioedema. Plasma kallikrein is a serine protease essential for the formation of bradykinin.

Multiphoton microscopy guides neurotrophin modification with poly(ethylene glycol) to enhance interstitial diffusion.

Brain-derived neurotrophic factor (BDNF) is a promising therapeutic agent for the treatment of neurodegenerative diseases. However, the limited distribution of this molecule after administration into the brain tissue considerably hampers its efficacy. Here, we show how multiphoton microscopy of fluorescently tagged BDNF in brain-tissue slices provides a useful and rapid screening method for examining the diffusion of large molecules in tissues, and for studying the effects of chemical modifications-for example, conjugating with polyethylene glycol (PEG)-on the diffusion constant.