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Drug Concentration in Blood |  |
| Drug concentrations in the blood can be determined and graphed against time. In most instances, the time course of a drug’s concentration in the plasma correlates well with the onset, intensity, and duration of the pharmacologic effect. Thus, the measurement of sequential plasma concentration of drugs after their administration is used to establish dosage regimens that are likely to produce the desired therapeutic levels for appropriate periods of time, without the risk of drug
failure or toxicity. |
| Single-dose Concentration Curves After Extravascular Administration: |
| When a drug is administered by an extravascular route, it usually appears in the plasma within a short time, and its concentration rises steadily until it peaks. Once absorbed into the circulation, it is subjected simultaneously to distribution, biotransformation, and excretion. During the initial period, the rate of absorption and distribution exceeds the rate of elimination. The peak plasma concentration is reached when absorption and elimination rates are equal. Thereafter,
the elimination rate exceeds the rate of absorption because less drug remains available at the site of administration, and plasma drug levels begin to fall. |
| The term “bioavailability” is used to express the rate and extent of absorption of a drug, usually from the GI tract after administration PO. Bioavailability is determined by administering equal doses of a drug by the IV (absorption effectively 100%) and PO routes and then comparing the areas under the 2 curves. Bioavailability is expressed as a percentage. The same principles can be applied to calculation of the bioavailability of drugs administered by other routes. |
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| Single-dose Concentration Curves After Intravascular Administration: |
| When a drug is administered by rapid IV injection, the maximum concentration in the blood is reached almost at once and immediately begins to fall. The profile of this decline can be determined by monitoring blood levels at periodic intervals and then plotting these concentrations against time. |
| From the single-dose concentration curves (extravascular and intravascular), a number of pharmacokinetic parameters can be calculated. These include the transfer rate constants between central and peripheral compartments; the elimination rate constant (Kel) for disappearance of drug from the central compartment; and the elimination half-life (t1/2), which has important clinical significance when determining dosing interval. |
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