Pharmacokinetics of Intravenously Administered 125I-Labelled Human α1-Acid Glycoprotein

Abstract

The volumes of distribution of many acidic drugs have been shown to be close to that of their binding protein, i.e. serum albumin. The distribution of basic drugs mainly bound to alpha 1-acid glycoprotein (AAG) can be questioned with respect to its dependency upon the distribution of this plasma protein. So, a pharmacokinetic study was performed in 7 subjects with human 125I-labelled alpha 1-acid glycoprotein. The steady-state volume of distribution was found to be 5.37 +/- 0.82L. The central volume was 3.23 +/- 0.33L, close to that of plasma volume and the peripheral volume was 2.14 +/- 0.63L. These data allowed the establishment of an equation giving access to the volume of distribution of a basic drug by relating its unbound fraction to physiological distribution of alpha 1-acid glycoprotein. The values yielded by this equation show that the actual and calculated volumes of distribution of basic drugs mainly bound to AAG are discrepant. This protein is thus not the main factor controlling the distribution of basic drugs within the body.

GlycA is a Novel Marker of Inflammation Among Non-Critically Ill Hospitalized Patients with Type 2 Diabetes

“…This is in contrast to other studies, mainly but not exclusively from acutely ill patients. [28, 29] One potential explanation for this may be that the stress hyperglycemic response is negligible in non-critically ill patients. Alternatively, stress hyperglycemia may depend upon patient characteristics.…”

“…Finally, inflammatory markers were typically drawn on the day after admission, potentially missing an important window of peak stress. While clearance of GlycA has not been well described, it would be expected to reflect that of the major protein glycans that are most likely to contribute to the NMR signal, such as α-1 acid glycoprotein (2-3 days) [29], α-1 antitrypsin (4-5 days) [30], and haptoglobin (5 days) [31]. Therefore, the GlycA signal at the time of the blood draw should reflect the time of admission, since patients were generally enrolled within one day of admission.…”

Clinical Pharmacokinetics of α1-Antitrypsin in Homozygous PiZ Deficient Patients

“…Such a model has been demonstrated for other serum proteins (Carlson et al 1985) such as albumin (Berson et al 1953), ai-acid glycoprotein (Bree et al 1986) and the vitamin D binding protein (Kawakami et al 1986). The 3-compartment model is confirmed by the external count of the labelled protein on different organs and by the pictures obtained after the whole body scintigraphy .…”

The impact of the concentration of drug binding plasma proteins on drug distribution according to Øie-Tozer’s model

“…Serum albumin and orosomucoid normally exist in plasma at a concentration of approximately 600 mmol/L and 25 mmol/L, respectively (Colombo et al, 2006;Kremer et al, 1988;Nicholson et al, 2000). In humans, the R E/I is estimated to 1.4 for serum albumin and 0.8 for orosomucoid (Brée et al, 1986;Waters & Lombardo, 2010). Using these four estimates, calculations using the suggested model were done for six hypothetical drugs (drug 1-6) of which drug 1, 3 and 5 had a k d of 20 mmol/L for serum albumin, and 0.6 mmol/L for orosomucoid, while drug 2, 4 and 6 only bind to serum albumin with a k d of 10 mmol/L.…”