Backgroud: To ensure the effect of renal function on drug exposure is precisely quantified, FDA guidance1recommends that studies recruit approximately equal subject numbers with normal renal function and mild, moderate and severe renal impairment. However, in population PK analyses it is common to pool data from various studies, resulting in an over-representation of subjects with normal […]
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Correlation in the absorption of lamivudine and zidovudine when administered as a fixed-dose combination tablet
Background: Lamivudine (3TC) and zidovudine (AZT) are potent selective inhibitors of HIV reverse transcriptase and, due to their synergistic effect, are available as a fixed dose combination (FDC) tablet for use in antiretroviral therapy (ART). The absorption and exposure of AZT and 3TC from single component and fixed-dose combination formulations are considered to be comparable. […]
Population pharmacokinetics of mycophenolic acid in children and young people undergoing bone marrow and solid organ transplantation
Background: Mycophenolate mofetil (MMF) is used as an immunosuppressant for the treatment and prevention of graft-versus host disease (GVHD) in bone marrow transplantation (Nash et al 2005) and acute graft rejection in solid organ transplantation (Srinivas et al 2003). Mycophenolic acid (MPA) is the active metabolite of MMF. MPA displays variability in treatment response which supports the need for individualised […]
Non Linear Deconvolution
Background: Deconvolution methods using stochastic differential equations have been investigated in publications [1,2,3]. Using this method the most likely outcome of an unobservable internal process can be quantified. The (extended) Kalman Filter is used for the quantification of the internal process which is based on the observations and the model specification. Examples are often simple linear […]
Pharmacokinetics of Ethanol in the Presence of Methanol
Background: In Australasia methanol overdoses are treated with high doses of ethanol. Appropriate dosing recommendations are lacking and in some cases dosing of ethanol is inadequate. There are no models for ethanol pharmacokinetics in the presence of methanol available in the literature. Aim: The overall aim is to develop dosing guidelines for ethanol treatment of […]
Population pharmacokinetics of phenobarbitone administered as oral rescue therapy in children with refractory status epilepticus
Background: Parenteral phenobarbitone, used in refractory status epilepticus, was unavailable in South Africafrom 2005 to 2006. Some centres supplemented status epilepticus management with a bolus of nasogastric phenobarbitone for children approaching refractory status. We assessed the efficacy, safety and phenobarbitone pharmacokinetics of this practice. Methods: Patients admitted in status epilepticus were enrolled unless impaired gastric absorption or […]
A model of coagulation disturbances in snake bites
Background: A procoagulant toxin (group C) is found in taipan (Oxyuranus genus) venom, which activates the coagulation cascade and causes venom induced consumptive coagulopathy (VICC). Objectives: To explore the turnover of the clotting factors in the coagulation cascade using a mathematical model and the effects of the procoagulant toxin on this system Evaluate the performance of the […]
Population pharmacokinetics of acyclovir in children with malignancy
Background: Acyclovir exhibits a selective inhibition of herpes virus replication with potent clinical antiviral activity against the herpes simplex and varicella-zoster virus (King & Madera, 1988).Valacyclovir, a pro-drug of acyclovir, increases the oral bioavailability of acyclovir (Soul-Lawton et al. 1995). Acyclovir is primarily renally eliminated. Acyclovir displays variability in treatment response which supports the need for individualised dose […]
Modeling Diverse Anti-Diabetic Drug Effects Using Indirect Response Models: Review
Background: Diabetes is a major health risk in many countries and incidence rates are increasing. Diverse anti-diabetic agents act through various mechanisms on different organs. A large array of mathematical models has been proposed to describe anti-diabetic drug effects. Objectives: 1) To systematically compare structural models that were used to model anti-diabetic drug effects. 2) To […]
Handling Correlated Variables
Many situations exist where multiple responses are measured during an experiment, e.g. parent and drug metabolite concentration and drug toxicity and efficacy. Typically the responses will be mixed (continuous and discrete) and display varying dependence structures. When standard multivariate distributions do not exist or are not applicable, a more flexible approach to the construction of […]