Inter-subject variability

Talbot RJ, Newton D, Priest ND, et al. 1995. Inter-subject variability in the metabolism of aluminum following intravenous injection as citrate. Hum Exp Toxicol 14 595-599. 

Ward SA, Watkins WM, Mberu E, et al. Inter-subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man. Br J Clin Pharmacol 1989 27 781-787. 

PK studies in the pediatric population are generally conducted in patients with the disease. This may lead to higher inter-subject variability than studies in healthy subjects, but the data better reflect clinical use. 

Mean small intestinal transit times for the Enterion capsule of 4.19 1.19, 4.69 1.71 and 4.11 1.45 h for Regimens B, C and D, respectively, are not unusual. There is always a high degree of intra- and inter-subject variability observed in gastrointestinal tract data. These intestinal transit times are in general agreement with the 3 h ( 1 h, range 1.3 to 6 h) previously reported for solutions, pellets and tablets. 

The PPK approach estimates the joint distribution of population specific pharmacokinetic model parameters for a given drug. Fixed effect parameters quantify the relationship e.g. of clearance to individual physiology like function of liver, kidney, or heart. The volume of distribution is typically related to body size. Random effect parameters quantify the inter-subject variability which remains after the fixed effects have been taken into account. Then the observed concentrations will still be randomly distributed around the concentration time course predicted by the model for an individual subject. This last error term called residual variability... 

Mitchell, D.Y., Barr, W.H., Eusebio, R.A., Stevens, K.A., Duke, F.P., Russell, D.A., Nesbitt, J.D., Powell, J.H., and Thompson, G.A. (2001). Risedronate pharmacokinetics and intra- and inter-subject variability upon single-dose intravenous and oral administration. Pharm Res 18 166-170. 

Thus, there does not appear to be a clear sex difference in the activity of the Phase I P450 isoenzymes discussed here. Most of the studies show wide inter subject variability in enzyme activity that is independent of sex. Furthermore, once data are controlled for age, weight, smoking status, and hormone use, there is little evidence for sex-dependent variability. In the future, large studies with genotype information and appropriate probe drugs will shed more light on this area. 

Erythromycin exhibits low oral bioavailability, low serum concentrations, a short in vivo half-life, and a high degree of intra- and inter-subject variability. Crystalline forms of erythromycin were found to be more bioavailable than amorphous forms [245]. TTie bioavailabilities of dirithro-mycin and erythromycin acistrate are increased by adding a basic substance such as a carbonate salt to the tablet or capsule [246, 247]. 

Differences between estimates can be also explained by inter-subject variability and age [15]. The scalp conductivity difference between SI and S2 is expected, as S2 is hairless. A hairless sealp is usually dryer and thus, less conductive. On the other hand, the skull thickness in SI is lower than in S2, implying less spongy bone (more conductive than compact bone) and a less conductive skull. 

Another interesting observation was that the breath concentrations taken over a period of time showed far less inter-subject variability than the concentrations determined from the blood measurements, which is speculated to be due to a large volume of blood having flowed through the lungs over the observation period. This inter-subject variability is illustrated... 

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