Steady-state volume of distribution

The recommended dose of pemetrexed is 500 mg/m2 administered as an intravenous infusion over 10 min on Day 1 of each 21-day cycle. Pemetrexed is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70-90% of the dose recovered unchanged within the first 24 h following administration. Pemetrexed has a steady-state volume of distribution of 16.1 L. Pemetrexed is highly bound (approximately 81%) to plasma proteins. Binding is not affected by the degree of renal impairment. Plasma... 

One solution to the volume problem was proposed using moment analysis. The steady-state volume of distribution (Vss) can be derived from the area under the curve (AUC) and the area under the first moment curve (AUMC). 

From the mean residence time MRT, the area under the curve AUC and the administered dose D, one can derive the steady-state volume of distribution of... 

The most important VD value for dictating the dosing regimen is the steady-state volume of distribution (VDSS). This volume represents the extent of distribution when the rate of transit to and from the tissues is equal. It is more representative of a time-averaged volume of distribution and its value will reside somewhere in between VDC and VDp. The steady-state VD is calculated from the mean-residence time (MRT). 

Distribution - Argatroban has an apparent steady-state volume of distribution is 174 mL/kg. It is 54% bound to human serum proteins. 

Alendronate - Mean steady-state volume of distribution (exclusive of bone) is 28 L or more. Protein binding in plasma is about 78%. 

Risedronate - The mean steady-state volume of distribution is 6.3 L/kg plasma protein binding is about 24%. Mean oral bioavailability is 0.63% and is decreased when administered with food. 

Carvedilol is more than 98% bound to plasma proteins (primarily albumin). It has a steady-state volume of distribution of approximately 115 L, indicating substantial distribution into extravascular tissues. Plasma clearance ranges from 500 to 700 mL/min. 

Pharmacokinetics The in vitro plasma protein binding of tigecycline ranges from approximately 71% to 89% at concentrations observed in clinical studies. The steady-state volume of distribution of tigecycline averaged 500 to 700 L (7 to 9 L/kg), indicating tigecycline is extensively distributed beyond the plasma volume and into the tissues. 

Distribution - The steady-state volume of distribution after IV administration was 0.74 L/kg. Cerebrospinal fluid concentrations obtained 0.25 and 5.67 hours post-dose in 3 patients who received 2.5 mg/kg ganciclovir IV every 8 or 12 hours ranged from 0.31 to 0.68 mcg/mL, representing 24% to 70% of the respective plasma concentrations. Binding to plasma proteins was 1 % to 2% over ganciclovir concentrations of 0.5 and 51 mcg/mL. 

Distribution - Plasma protein binding of ganciclovir is 1% to 2%. When ganciclovir was administered IV, the steady-state volume of distribution of ganciclovir was about 0.703 L/kg (n = 69). 

The steady-state volume of distribution following IV administration of a 1.5 mg dose averaged 0.534 L/kg. Cerebrospinal fluid obtained from 9 patients at 2 to 3.5 hours following 0.06 or 0.09 mg/kg IV infusion showed measurable concentrations of zalcitabine. The CSFiplasma concentration ratio ranged from 9% to 37% (mean, 20%), demonstrating drug penetration through the blood-brain barrier. 

Mean serum clearance values ranged from 9.4 to 28.9 mL/min/kg and were independent of dose. Mean terminal elimination half-life values ranged from 8 minutes to 4.3 hours and mean steady-state volume of distribution values ranged from 0.25 to 2.88 L/kg. IV dosing 3 times/week for 2 weeks resulted in no accumulation of interferon beta-la or beta-lb in the serum of patients. 

The volume of distribution is a parameter that can be calculated from plasma drug concentration versus time data (expressed as area under the curve or AUC), according to the two equations shown below, for terminal or steady-state volume of distribution, respectively. 

Abbreviations include PT, preterm neonate T, term neonate Vj gg, apparent steady state volume of distribution and tij2, half-Ufe. 

Pharmacokinetics Complete and consistent blocking of the IL-2 receptor is maintained as long as serum basiliximab levels exceed 0.2pg/ml. As concentrations fall below this level, expression of IL-2 receptor returns to pre-therapy values within 1-2 weeks. Basiliximab has a steady-state volume of distribution of 9 liters and total body clearance of 41 ml/h. Its elimination half-life ranges from 7 to 10 days. There is a dose-proportional increase in peak concentration (Cmax) and area under the curve (AUC) up to the highest tested single dose of 60 mg. No clinically relevant influence of body weight or gender on distribution volume or clearance has been observed in adult patients. Elimination... 

N. Watari and L. Z. Benet. Determination of mean input time, mean residence time, and steady-state volume of distribution with multiple drug inputs. J. Pharm. Biopharm. 17 593-599, 1989. 

The steady-state volume of distribution is 12 1/kg. Donepezil hydrochloride is approximately 96% bound to human plasma proteins. The distribution of donepezil hydrochloride in various body tissues has not been definitively studied. However, in a mass balance study conducted in healthy male volunteers, 240 h after the administration of a single 5 mg dose of 14C-labeled donepezil hydrochloride, approximately 28% of the label remained unrecovered. This suggests that donepezil and/or its metabolites may persist in the body for more than 10 days. 

In general, the volume of distribution of the central compartment (Vc), in which peptides and proteins initially distribute after an IVadministration, is typically equal to or slightly larger than the plasma volume of 3-8 L (approximate body water volumes for a 70-kg person interstitial 12 L, intracellular 27 L, intravascular 3 L). Furthermore, the steady-state volume of distribution (Vss) is usually no more than twice the initial volume of distribution, or approximately 14-20 L [13, 37, 43]. This distribution pattern has been described for the somatostatin analogue octreotide (Vc 5.2-10.2 L Vss 18-30 L), and t-PA analogue tenecteplase (Vc 4.2-6.3 L Vss 6.1-9.9 L) [52]. Epoetin-a also has a volume of distribution estimated to be close to the plasma volume at 0.0558 L/kg after an IVadministration to healthy volunteers [53]. Similarly, Vss for darbepoetin-a has been reported as 0.0621 L/kg after an IV administration in patients undergoing dialysis [54], and distribution of thrombopoie-tin has also been reported to be limited to the plasma volume (-3 L) [55]. 

Benet, L.Z., and R.L. Galeazzi. 1979. Noncompartmentai determination of the steady-state volume of distribution. 

V, steady-state volume of distribution referenced to the unbound drug in plasma. Kp, partition coefficient of drug between plasma protein and plasma water, r, ratio of the fractions of the drug non renally and renally eliminated. 

Tab. 4.28 Comparison of membrane-predicted and literature values of steady-state volumes of distribution (VuSS) of p-blockers. (Reprinted from Tab. 6 of ref. 93, with permission from Elsevier...

A review of the effects of obesity on drug pharmacokinetics briefly mentioned that the steady-state volume of distribution of lithium correlated with ideal body weight and fat-free mass but not with total body weight (514). Lithium clearance was greater in those with obesity than in lean controls, suggesting that obese patients may require larger maintenance doses to maintain target serum concentrations. 

---