Pharmaeokineties, PK: Absorption, distribution, metabolism and excretion of drugs in the body and their time course.
Pharmacodynanfics, PD: Describe the effect of drugs on the body, that is, the kinetic process of the effect changing with time and concentration (more clinically meaningful than the former).
For quite a long period of time, the research on the two was carried out separately, and the inner relationship between the two was ignored, which made the research on PK and PD have certain limitations.
On the one hand, PK research is only meaningful if the relationship between drug concentration and effect is understood;
On the other hand, PD research does not take into account the impact of the dynamic changes of drugs in the body on the intensity and duration of drug effects, so the information obtained is also incomplete.
PK-PD binding model
PK: The effect of the body on the drug
PD: the effect of the drug on the body PK/PD: the time-effect course of a given dose
– PK/PD is a comprehensive study of the kinetic process of drugs in vivo and the kinetic process of quantitative indicators of drug efficacy
– The essence of the PD/PK binding model is to study a process of conversion between drug dose and effect
Purpose of PD/PK
– The purpose of PK/PD research is to determine the relationship between drug dose, concentration in body fluids and the intensity and time of drug action
– The most widely used is the evaluation of antibacterial drugs
– The application of PK-PD model is beneficial to the dose design and dose adjustment of clinical pharmacy, and it is the most reasonable explanation for the anti-infection treatment of different patient groups
Application purpose of PK/PD
– Phase 2-3 clinical trial
– Improvement of therapy
The relationship between pharmacodynamics, pharmacokinetics and curative effect
– Pharmacokinetics PK is concerned with the process of antibiotic concentration in the body, while pharmacodynamics PD is concerned with the relationship between drug concentration and antibacterial activity;
– The traditional method of antibiotic dosing regimen is only determined by measuring PK parameters;
– In recent years, due to the increasing number of drug-resistant strains, PD has become more important, because PD parameters are very important for the formulation of drug regimens to prevent the emergence of drug resistance;
– The most important parameter for measuring antibiotic activity in PD is MIC;
– MIC is the in vitro bacteriostatic activity;
– Although MIC is the best indicator of the strength of antibiotic action, it does not reflect the relationship between this activity and time
– PK can quantify the relationship between blood drug concentration and time, and has three parameters: Cmax; Cmin; AUC
– but these parameters do not describe the bactericidal activity of the antibiotic
– Bioavailability (F)
– Peak concentration (Cmax, Cpeak)
– Time to peak (Tmax or Tpeak)
– Apparent volume of distribution (Vd)
– half-life (T1/2)
– Clearance (CL)
– Elimination rate constant (Ke)
– Area under the plasma concentration-time curve (AUC)
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PK driven SAR has become the new trends for lead optimizations. More and more companies are including a PK team within their medicinal chemistry division. However, the time and cost for initiating and maintaining such a program can be very costly that may not feasible at all for a small company. At AxisPharm, we can function just like your own pre-clinic PK team at a small fraction of cost compare with building such as team in house. Our expertise, experiences, and instrumentation are all within your reach.
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