First human administration of a new chemical entity (NCE) constitutes a critical step in drug development. The primary objective of such a study is the assessment of the shortterm safety and tolerability of single and multiple doses of the NCE in healthy volunteers. Secondary objectives are to obtain preliminary data on the pharmacokinetics and pharmacodynamics using surrogate or biornarkers of...

Purpose: GDC-0973 is a potent and selective mitogen-activated protein (MAP)/extracellular signal– regulated kinase (ERK) kinase (MEK) inhibitor. Pharmacokinetic–pharmacodynamic (PK–PD) modeling was used to relate GDC-0973 plasma and tumor concentrations, tumor pharmacodynamics and antitumor efficacy to establish pharmacokinetic endpoints and predict active doses in the clinic. ExperimentalDesig...

Interindividual variability in immunosuppressive drug responses might be partly explained by genetic variants in proteins involved in the immune response or associated with IS pharmacodynamics. On a general basis, the pharmacogenetics of drug target proteins is less known and understood than that of proteins involved in drug disposition pathways. The aim of this review is to facilitate research...

OBJECTIVE To assess the role of adiposity on the pharmacodynamics of basal insulins NPH, detemir, and glargine in type 2 diabetes mellitus (T2DM), as estimated by glucose infusion rate (GIR) and endogenous glucose production (EGP) rate in the euglycemic clamp. RESEARCH DESIGN AND METHODS We examined the variables that best predicted GIR and EGP in 32-h clamp studies after treatment with subcu...

The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment gro...

Pharmacokinetics and pharmacodynamics of the long-acting insulin analog glargine (1) are superior to those of insulin NPH (2–9). In the clinical setting, this translates into lower risk of nocturnal hypoglycemia (10–13), lower A1C (provided that appropriate requirements of mealtime rapid-acting insulin are met) (11–13), and the convenience of once (12), compared with multiple, administration of...

This article summarizes the impact of the pharmacogenetics of drug transporters expressed in the enterohepatic circulation on the pharmacokinetics and pharmacodynamics of drugs. The role of pharmacogenetics in the function of drug transporter proteins in vitro is now well established and evidence is rapidly accumulating from in vivo pharmacokinetic studies, which suggests that genetic variants ...

We have studied the effect of renal function on the pharmacodynamics of mivacurium. Sixty patients were allocated to three groups according to creatinine clearance: group C (control), creatinine clearance > 50 ml min-1; group P (preterminal renal failure), creatinine clearance < 50 ml min-1 > 20 ml min-1; group T(terminal renal failure), creatinine clearance < 20 ml min-1. Neuromuscular transmi...

Isavuconazonium sulfate is a novel triazole prodrug that has been recently approved for the treatment of invasive aspergillosis by the FDA. The active moiety (isavuconazole) has a broad spectrum of activity against many pathogenic fungi. This study utilized a dynamic in vitro model of the human alveolus to describe the pharmacodynamics of isavuconazole against two wild-type and two previously d...

Two types of antiviral treatments, namely, interferon and nucleoside/nucleotide analogues are available for hepatitis infections. The selection of drug and dose determined using known pharmacokinetics and pharmacodynamics data is important. The lack of sufficient information for pharmacokinetics of a drug may not produce the desired results. Artificial neural network (ANN) provides a novel mode...