Variability inter-patient

Fluoropyrimidines (e.g., 5-FU, oral capecitabine) remain unchallenged as reference drugs for treating munerous solid tumors in adults, including digestive, head and neck, and breast cancers. The wide inter-patient variability observed in the pharmacokinetic profiles of these drugs is mainly caused by the erratic activity of dihydropyrimidine... 

Marked inter-patient variability exists in the pharmacokinetics of intravenous anaesthetics. Factors that can influence drug disposition include the degree of protein binding, the efficiency of the hepatic and renal clearance systems, physiological changes with ageing, disease states, site of operation, body temperature, and drug interactions (premedicants, volatile anaesthetics). 

The statistical submodel characterizes the pharmacokinetic variability of the mAb and includes the influence of random - that is, not quantifiable or uncontrollable factors. If multiple doses of the antibody are administered, then three hierarchical components of random variability can be defined inter-individual variability inter-occasional variability and residual variability. Inter-individual variability quantifies the unexplained difference of the pharmacokinetic parameters between individuals. If data are available from different administrations to one patient, inter-occasional variability can be estimated as random variation of a pharmacokinetic parameter (for example, CL) between the different administration periods. For mAbs, this was first introduced in sibrotuzumab data analysis. In order to individualize therapy based on concentration measurements, it is a prerequisite that inter-occasional variability (variability within one patient at multiple administrations) is lower than inter-individual variability (variability between patients). Residual variability accounts for model misspecification, errors in documentation of the dosage regimen or blood sampling time points, assay variability, and other sources of error. 

Hence, due to a two-fold increase in AUC and less inter-patient variability compared with omeprazole and concomitant superior acid inhibition and higher predictability, esomeprazole, the S-isomer of omeprazole (in alkaline salt form), provides clinical benefit in a wide range of acid-related disorders. 

Despite the efficacy of the PPIs, there is still potential for clinical improvement in GERD pharmacotherapy [46]. A faster onset of complete acid inhibition, a lower inter-patient variability in the inhibition of acid secretion, and an improved duration of efficacy are potential areas for improvement [47]. Concomitant antacid use among PPI users (37%) suggests that current therapies may not always achieve sufficient acid control when used as monotherapy for GERD [48]. 

Discuss the inter-patient variability of orally administered propafenone. 

It is suggested that the interaction is caused by the enzyme inhibitory ae-tions of cimetidine, which result in a reduetion in the metabolism of albendazole and mebendazole. Cimetidine may also reduee albendazole absorption and minimise inter-patient variability by redueing gastrie aeid-ity, but the reduction in absorption appears to be outweighed by the enzyme-inhibitory effects. 

Seven patients with chronic hepatitis C receiving interferon beta 3 to 9 million units daily for 8 weeks were given a single 250-mg dose of intravenous aminophylline. Interferon beta reduced the total body clearance of theophylline by 26% (range 5.8 to 57%) and increased the elimination half-life by 39% (range 27 to 139%), but had no significant effect on the volume of distribuhon, although there was wide inter-patient variability. ... 

The density of this fluid also shows intra- and inter-patient variability (Fig. 4.14). 

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