noncompartmental

Noncompartmental analysis (NCA) is a pharmacokinetic data analysis approach that characterizes the disposition of a drug using observed concentration–time data without assuming a specific compartmental model. It is considered model-independent and focuses on descriptive, rather than mechanistic, properties of drug exposure and elimination.

In NCA, the primary quantities are derived directly from the concentration–time data. The area under the concentration–time curve (AUC) is calculated by the trapezoidal rule, and AUC can be extrapolated to infinity using the terminal elimination rate constant (λz). The terminal slope of the log concentration versus time line provides λz, from which the elimination half-life t1/2 is computed as ln(2)/λz. The mean residence time (MRT) is obtained as the ratio of the first moment AUMC to AUC, where AUMC is the area under the curve of time multiplied by concentration. Observed maximum concentration (Cmax) and time of maximum concentration (Tmax) are reported from the data, when available.

Clearance and volume terms in NCA are summary parameters derived from AUC and dose. For intravenous dosing, clearance is estimated as Dose/AUC0–∞. For extravascular dosing, clearance is reported as CL/F = Dose/AUC0–∞, where F is bioavailability. The apparent volume of distribution is often reported as Vd = CL × MRT, with Vd/F used for non–intravenous dosing.

Applications and limitations: NCA is widely used in early pharmacokinetic studies and clinical pharmacology to provide quick, model-free summaries of drug exposure. Limitations include reliance on adequate sampling, especially in the terminal phase, and the assumption of linear pharmacokinetics. NCA does not reveal underlying mechanisms or compartment structure and can be sensitive to sampling design and extrapolation.