## Table 4 |
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In vivo PK studies |
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Category |
Name |
Description |
Unit |
reference |

PK parameters | AUC_{inf} |
Area under the drug concentration time curve. | mg h L^{-1} |
RT p37 |

AUC_{SS} |
Area under the drug concentration time curve within a dosing curve at steady state. | mg h L^{-1} |
RT pxi | |

AUC_{t} |
Area under the drug concentration time curve from time 0 to t. | mg h L^{-1} |
RT p37 | |

AUMC | Area under the first moment of concentration versus time curve. | mg^{2} h L^{-2} |
RT p486 | |

AUCR | AUC ratio (drug interaction parameter). | Unit free | ||

CL | Total clearance is defined as the proportionality factor relating rate of drug elimination to the plasma drug concentration. | ml h^{-1} |
RT p23 | |

CL_{b} |
Blood clearance is defined as the proportionality factor relating rate of drug elimination to the blood drug concentration. | ml h^{-1} |
RT p160 | |

CL_{u} |
Unbound clearance is defined as the proportionality factor relating rate of drug elimination to the unbounded plasma drug concentration. | ml h^{-1} |
RT p163 | |

CL_{H} |
Hepatic portion of the total clearance. | ml h^{-1} |
RT p161 | |

CL_{R} |
Renal portion of the total clearance. | ml h^{-1} |
RT p161 | |

CL_{po} |
Total clearance of drug following an oral dose. | ml h^{-1} |
||

CL_{IV} |
Total clearance of drug following an IV dose. | ml h^{-1} |
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CL_{int} |
Intrinsic metabolic clearance is defined as ratio of maximum metabolism rate, Vmax, and the Michaelis-Menten constant, Km. | ml h^{-1} |
RT p165 | |

CL_{12} |
Inter-compartment distribution between the central compartment and the peripheral compartment. | ml h^{-1} |
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CL ratio | Ratio of the clearance (drug interaction parameter). | Unit free | ||

C_{max} |
Highest drug concentration observed in plasma following administration of an extravascular dose. | mg L^{-1} |
RT pxii | |

C_{max} ratio |
The ratio of C_{max} (drug interaction parameter). |
Unit free | ||

C_{ss} |
Concentration of drug in plasma at steady state during a constant rate intravenous infusion. | mg L^{-1} |
RT pxii | |

C_{ss} ratio |
The ratio of C_{ss} (drug interaction parameter). |
Unit free | ||

E | Extraction ratio is defined as the ratio between blood clearance, CL_{b}, and the blood flow. |
Unit free | RT p159 | |

E_{H} |
Hepatic extraction ratio. | Unit free | RT p161 | |

F | Bioavailability is defined as the proportion of the drug reaches the systemic blood. | Unit free | RT p42 | |

F_{G} |
Gut-wall bioavailability. | Unit free | ||

F_{H} |
Hepatic bioavailability. | Unit free | RT p167 | |

F_{R} |
Renal bioavailability. | Unit free | RT p170 | |

fe | Fraction of drug systemically available that is excreted unchanged in urine. | Unit free | RT pxiii | |

fm | Fraction of drug systemically available that is converted to a metabolite. | Unit free | RT pxiii | |

fu | Ratio of unbound and total drug concentrations in plasma. | Unit free | RT pxiii | |

k | Elimination rate constant. | h^{-1} |
RT pxiii | |

K_{12}, k_{21} |
Distribution rate constants between central compartment and peripheral compartment. | h^{-1} |
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ka | Absorption rate constant. | h^{-1} |
RT pxiii | |

ke | Urinary excretion rate constant. | h^{-1} |
RT pxiii | |

km | Rate constant for the elimination of a metabolite. | h^{-1} |
RT pxiii | |

Km | Michaelis-Menten constant. | mg L^{-1} |
RT pxiii | |

MRT | Mean time a molecular resides in body. | h | RT pxiv | |

Q | Blood flow. | L h^{-1} |
RT pxiv | |

Q_{H} |
Hepatic blood flow. | L h^{-1} |
RT pxiv | |

t_{max} |
Time at which the highest drug concentration occurs following administration of an extravascular dose. | h | RT pxiv | |

t_{1/2} |
Half-life of the drug disposition. | h | RT pxiv | |

t_{1/2} ratio |
Half-life ratio (drug interaction parameter). | Unit free | ||

t_{1/2,α} |
Half-life of the fast phase drug disposition. | h | ||

t_{1/2,β} |
Half-life of the slow phase drug disposition. | h | ||

V | Volume of distribution based on drug concentration in plasma. | L | RT pxiv | |

V_{b} |
Volume of distribution based on drug concentration in blood. | L | RT pxiv | |

V_{1} |
Volume of distribution of the central compartment. | L | RT pxiv | |

V_{2} |
Volume of distribution of the peripheral compartment. | L | ||

V_{ss} |
Volume of distribution under the steady state concentration. | L | RT pxiv | |

Vmax | Maximum rate of metabolism by an enzymatically mediated reaction. | mg h^{-1} |
RT pxiv | |

λ_{1}, λ_{2} |
Disposition rate constants in a two-compartment model. | h^{-1} |
GP p84 | |

Pharmacokinetics Models | Non-Compartment | Use drug concentration measurements directly to estimate PK parameters, such as AUC,
CL, C_{max}, T_{max}, t_{1/2}, F, and V. |
GP p409 | |

One Compartment Model | It assumes the whole body is a homogeneous compartment, and the distribution of the drug from the blood to tissue is very fast. It assumes either a first order or a zero order absorption rate and a first order eliminate rate. Its PK parameters include (ka, V, CL, F). | RT p34 | ||

GP p1 | ||||

Two Compartment Model | It assumes the whole body can be divided into two compartments: central compartment
(i.e. systemic compartment) and peripheral compartment (i.e. tissue compartment).
It assumes either a first order or a zero order absorption rate and a first order
eliminate and distribution rates. Its PK parameters include (ka, V_{1}, V_{2}, CL, CL_{12}, F). |
GP p84 | ||

Study Designs | Hypothesis | Bioequivalence, drug interaction, pharmacogenetics, and disease conditions. | ||

Design | Single arm or multiple arms; cross-over or fixed order design; with or without randomization; with or without stratification; prescreening or no-prescreening; prospective or retrospective studies; and case reports or cohort studies. | |||

Sample size | The number of subjects, and the number of plasma or urine samples per subject. | |||

Time points | Sampling time points and dosing time points. | |||

Sample types | Blood, plasma, and urine. | |||

Dose | Subject specific doses. | |||

Quantification methods | HPLC/UV, LC/MS/MS, LC/MS, radiographic |

Rowland Malcolm and Tozer N. Thomas Clinical Pharmacokinetics Concepts and Applications,
3^{rd} edition. 1995, Lippincott Williams & Wilkins.

Gibaldi Milo and Perrier Donald. Pharmacokinetics, 2^{nd} edition. 1982, Dekker.

Wu * et al.*

Wu * et al.* *BMC Bioinformatics* 2013 **14**:35 doi:10.1186/1471-2105-14-35