Plasma Protein Binding of Lidocaine and Warfarin in Insulin-Dependent and Non-Insulin-Dependent Diabetes Mellitus

Abstract

We examined the plasma protein binding of an acidic drug (warfarin bound to albumin) and a basic drug [lidocaine (lignocaine) bound to alpha 1-acid glycoprotein] in 15 patients with insulin-dependent diabetes mellitus (IDDM) and 15 matched controls. We also examined protein binding of warfarin and lidocaine in 30 patients with non-insulin-dependent diabetes (NIDDM) and 25 controls. Compared with control, the binding of both warfarin (98.81 +/- 0.02 vs 98.57 +/- 0.03%, mean +/- SEM) and of lidocaine (69 +/- 2 vs 58 +/- 2%) was significantly reduced in IDDM. This group had lower concentrations of both albumin and alpha 1-acid glycoprotein (AAG), achieving statistical significance vs control for albumin only. In the patients with NIDDM, who had a similar level of glycosylated haemoglobin, while there was no significant difference in the binding of lidocaine there was a significant increase in warfarin binding compared with the control population (99.01 +/- 0.03 vs 98.82 +/- 0.04%). This study suggests that binding of both acidic and basic drugs is altered in both IDDM and NIDDM.

Subtherapeutic Anticoagulation Control under Treatment with Vitamin K-Antagonists—Data from a Specialized Coagulation Service

“…26,27 The independent and strong risk of diabetics for INR control below the therapeutic range has been discussed earlier and may be mediated by the influence of insulin-and noninsulindependent diabetes on plasma protein binding of acidic drugs, such as VKA. 28 As reported previously by others, diabetes was independently associated with poorer anticoagulation control and outcome in patients with atrial fibrillation. 29,30 The present study, however, extends this knowledge to a real-world sample which is unselected for the indication for OAC therapy.…”

Effects of type 1 and type 2 diabetes on the pharmacokinetics of tramadol enantiomers in patients with neuropathic pain phenotyped as cytochrome P450 2D6 extensive metabolizers

“…The inconsistency observed on fraction unbound of (+)‐M1 when comparing T1DM and T2DM was also observed for both acidic and basic drugs in previous studies described in the literature. The fraction unbound of lidocaine and warfarin was increased in patients with T1DM compared with nondiabetics, but not in patients with T2DM [40]. Thus, in addition to the nonenzymatic glycation of plasma proteins, the influence of diabetes on fraction unbound seems to be due to the lower levels of albumin and α 1 ‐acid glycoprotein in T1DM but not in T2DM, when compared with nondiabetic patients [40]…”

The Effects of Diabetes Mellitus on Pharmacokinetics and Pharmacodynamics in Humans

“…Since the degree of glycosylation is a measure of the exposure of the protein to sustained glucose concentrations, glycosylated haemoglobin is used as an index of diabetic controL Several authors have reported correlations between the degree of glycosylation and serum drug binding. Mereish and co-workers (1982) (1984) 7.6 ± 1.6d Gatti et al (1987) 1.43 ± 0.3d Barry et al (1986) 1.0 ± 0.03 O'Byrne et al (1988) tions, and found that the binding of salicylate decreased with glycosylation. They point out, however, that the glycosylated fraction comprises a relatively small proportion of total albumin and even at 25 to 30% glycosylation (the highest values generally seen in diabetic patients), there was no significant decrease in the salicylate binding capacity.…”

“…One further point of interest found in table II is the difference in the binding of warfarin and lidocaine (lignocaine) between patients with 100M and those with NIDOM (Barry et al 1986;O'Byrne et al 1988). In the former group, the binding of lidocaine and warfarin decreased by 37 and 20%, respectively, whereas in the latter group no change in binding was observed.…”