Elimination drugs

Drug elimination may not be first order at high doses due to saturation of the capacity of the elimination processes. When this occurs, a reduction in the slope of the elimination curve is observed since elimination is governed by the relationship Vmax/(Km- -[conc]), where Vmax is the maximal rate of elimination, Km is the concentration at which the process runs at half maximal speed, and [cone] is the concentration of the drug. However, once the concentration falls below saturating levels first-order kinetics prevail. Once the saturating levels of drugs fall to ones eliminated via first-order kinetics, the half time can be measured from the linear portion of the In pt versus time relationship. Most elimination processes can be estimated by a one compartment model. This compartment can... 

First order kinetics describes the most common time course of drug elimination. The amount eliminated within a time-interval is proportionate to the drug concentration in the blood. 

The effect of hemofiltration on drug elimination can be estimated from serum creatinine (SCr), age, and the MDRD-2 formula to predict the combined effect of filtration rate (eGFR = GFRresidual + HFR) on drug clearance and drug half-life during hemofiltration. 

Affecting the rate of drug elimination by increasing urinary pH (eg, the excretion of salicylates is increased, whereas excretion of quinidine and amphetamines is decreased)... 

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

III. FIRST-ORDER PHARMACOKINETICS DRUG ELIMINATION FOLLOWING RAPID INTRAVENOUS INJECTION... 

It was mentioned previously that drug elimination from the body most often displays the characteristics of a first-order process. Thus, if a drug is administered by rapid intravenous (IV) injection, after mixing with the body fluids its rate of elimination from the body is proportional to the amount remaining in the body. 

A clearance rate is defined as the volume of blood or plasma completely cleared of drug per unit time. It is a useful way to describe drug elimination because it is related to blood or plasma perfusion of various organs... 

The glomerular filtration rate (GFR) in normal males is estimated to be 125mL/min, and the results of the example calculation suggest that the drug is cleared by GFR. If the RCR had been less than 125 mL/min, tubular reabsorption of the drug would have been suspected. If it had been greater than 125 mL/min, tubular secretion would have been involved in the drug elimination. 

VI. PHARMACOKINETICS OF DRUG ELIMINATED BY SIMULTANEOUS METABOLISM AND EXCRETION... 

The Wagner-Nelson method of calculation does not require a model assumption concerning the absorption process. It does require the assumption that (a) the body behaves as a single homogeneous compartment and (b) drug elimination obeys first-order kinetics. The working equations for this calculation are developed next. 

The mass transfer coefficients may also be expressed in units of time-1 by multiplying by the appropriate compartmental volume term. Irreversible drug elimination from the tissue requires the addition of an expression to the differential equation that represents the subcompartment in which elimination occurs. For instance, hepatic drug elimination would be described by a linear or nonlinear expression added to the intracellular liver compartment mass balance equation since this compartment represents the hepatocytes. Formal elimination terms are given below for the simplified tissue models. 

Drug elimination from a membrane-limited tissue compartment requires subtraction of the rate of elimination, qh from the appropriate mass balance equation, typically from subcompartment 2. 

Pharmacy application lipid solubility and drug elimination... 

Within the OAT family, OAT4 is the only transporter expressed at appreciable levels in both the placenta and in the kidney [54]. The membrane localization of OAT4 within these tissues has not been examined. Steroid sulfates, and ochratoxinA are efficient transport substrates of OAT4, whereas PAH is weakly transported [54]. The functional importance of OAT4 in regulating placental permeability and renal drug elimination is currently unknown. 

Can be engineered to be Drug elimination is critical element of design... 

At 2 h after dosing, the plasma concentration was 4.6 mg/mL at 5 h, the concentration was 2.4 mg/mL. Therefore, the plasma concentration of this aminoglycoside decreased to one-half in approximately 3 h—its half-life. In addition, drug elimination usually occurs according to first-order kinetics (i.e., a linear relationship is obtained when the drug concentration is plotted on a logarithmic scale vs. time on an arithmetic scale (a semilogarithmic plot)]. 

The plasma concentration will continue to rise until it reaches a plateau, or steady state. At this time, the plasma concentration will fluctuate between a maximum (Cmav) and a minimum (CrnLn) level, but, more important, the amount of drug eliminated per dose interval will equal the amount of drug absorbed per dose. When a drug is given at a dosing interval that is equal to its elimination half-life, it will reach 50% of its steady-state plasma concentration after one half-life, 75% after two half-lives, 87.5% after three, 93.75% after four, and 96.87% after five. Thus, from a practical viewpoint,... 

Accelerated drug elimination is also a possible reason for failure and may occur in patients with cystic fibrosis or during pregnancy, when more rapid clearance or larger volumes of distribution may result in low serum concentrations, particularly for aminoglycosides. 

Methods for calculating volume of distribution (VD) can be influenced by renal disease. Of the commonly used terms (i.e., volumes of central compartment, terminal phase, and distribution at steady state [ Vss]), Vss is the most appropriate for comparing patients with renal insufficiency versus those with normal renal function because Vss is independent of drug elimination. 

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