Intravenous bolus clearance

There is substantial variability in the pharmacokinetics of vinblastine in patients. Evidence has been obtained that implicates altered liver function and dose-dependent elimination as contributing factors to the variable pharmacokinetics. When vinblastine was administered by a bolus injection, a mean terminal elimination half-life of 29.2 hr was estimated for a group of 24 patients, but the half-lives ranged from a low value of 16 hr to a high value of 65 hr (55). When vinblastine was administered by intravenous infusion, clearance of the drug appeared to decrease with time over a 4-month period decreases in serum albumin values were found to be correlated with decreases in the clearance of vinblastine. 

Pharmacokinetics The bioavailability of a subcutaneous dose of epoetin alfa, relative to an intravenous bolus, has been estimated at 22% to 31%. The elimination half-life of epoetin alfa after an intravenous dose is 6 to 13 hours in patients with chronic renal failure. Mean clearance ranges from 0.032 to 0.055 ml/min per kg. The apparent half-life after a subcutaneous dose is 27 hours. Volume of distribution estimates range from 0.021 to 0.0631/kg. 

Finally, the method used to calculate the volume of distribution may be influenced by renal insufficiency. The three most commonly used volume of distribution terms are volume of the central compartment (Ec), volume of the terminal phase (E, E jea). and volume of distribution at steady state (Eis). The central compartment volume is calculated as the intravenous bolus dose divided by the initial plasma concentration. E for many drugs approximates extracellular fluid volume and thus may be increased or decreased by shifts in this physiologic volume. Renal insufficiency, especially oliguric acute renal failure, is often accompanied by fluid overload and a resultant increased Ec due to reduced renal elimination of water and sodium. Uaiea Or E is Calculated as the total body clearance divided by the terminal elimination rate constant (k or /3). This volume term represents the proportionality constant between plasma concentrations in the terminal elimination phase and the amount of drug remaining in the body. E is affected by both distribution characteristics, as well as by the elimination rate constant. The third volume term, the steady-state volume of distribution (Ess), is calculated as (AUMC x dose)/AUC , where AUMC is the area under the first moment of the concentrationtime curve and AUC is the area under the concentration-time curve... 

Renal clearance of intravenous bolus of drug (one compartment]... 

Intravenous bolus 15 to 60 mg/m s then 15 to 60 mg/m intravenous infusion over 36 hours Dicloxacillin (not stated) (Indometacin ako given) Oesophageal cancer (1) 93% reduction in methotrexate clearance prolonged folinic acid rescue necessary 3... 

A 40% decrease in the clearance of a 2-mg intravenous bolus dose of lorazepam was seen in 6 out of 8 healthy subjects while they were taking valproate 250 mg twice daily. A woman taking valproate, phenytoin, and carbamazepine went into a coma after she received a total of 6 mg of intravenous lorazepam. She promptly recovered on stopping the valproate. ... 

In a placebo-controlled study in 12 healthy subjects, intravenous pantoprazole 240 mg for 7 days did not change the half-life, clearance and AUC of a 100-microgram/kg intravenous bolus dose of diazepam."... 

Remifentanil binds to and activates p receptors in the brain and spinal cord. It is generally administered as an intravenous bolus or continuous infusion. The average clearance of remifentanil in young healthy adults generally correlates with total body weight in severely obese patients it correlates with ideal body weight. Blood concentration decreases 50% in 3 to 6 minutes after cessation of infusion and clinical recovery from the effects occurs rapidly, within 5 to 10 minutes. The terminal half-life is 10 to 20 minutes. Distinct from other opioids in its class, the duration of action does not increase with prolonged administration [1,2]. 

An easy and rapid method with intravenous bolus administration of an iohexol/ PAH mixture in dogs has been developed for simultaneous measurement of GFR and eRPF, based on plasma clearances of both substances (Laroute et al. 1999). 

Seddon et al. (1980) studied the pharmacokinetics of ceftriaxone in humans (Table XII). Six male volunteers received a 500-mg intravenous bolus injection of ceftriaxone. Mean serum concentrations of 93 p,g/ml were measured 10 min after dosing. After a rapid distribution phase, the elimination half-life was 8.8 hr. Total urinary recovery after 48 hr was 58% the remainder was eliminated via biliary secretion. Metabolism is minimal. The serum clearance of ceftriaxone is only about 1% of the glomerular filtration rate, suggesting that there is no tubular secretion of this drug. Wise et al. (1980c) reported that ceftriaxone was 95% protein bound in humans. 

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