Pharmacokinetics, sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption Drug Absorption Drug absorption is determined by the drug’s physicochemical properties, formulation, and route of administration. Dosage forms (eg, tablets, capsules, solutions), consisting of the drug plus... read more , bioavailability Drug Bioavailability Bioavailability refers to the extent and rate at which the active moiety (drug or metabolite) enters systemic circulation, thereby accessing the site of action. Bioavailability of a drug is... read more , distribution Drug Distribution to Tissues After a drug enters the systemic circulation, it is distributed to the body’s tissues. Distribution is generally uneven because of differences in blood perfusion, tissue binding (eg, because... read more , metabolism Drug Metabolism The liver is the principal site of drug metabolism (for review, see [ 1]). Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active—sometimes even... read more , and excretion Drug Excretion The kidneys are the principal organs for excreting water-soluble substances. The biliary system contributes to excretion to the degree that drug is not reabsorbed from the gastrointestinal ... read more . Show
Pharmacokinetics of a drug depends on patient-related factors as well as on the drug’s chemical properties. Some patient-related factors (eg, renal function, genetic makeup, sex, age) can be used to predict the pharmacokinetic parameters in populations. For example, the half-life of some drugs, especially those that require both metabolism and excretion, may be remarkably long in older people (see figure Comparison of pharmacokinetic outcomes for diazepam in a younger man [A] and an older man [B] Comparison of pharmacokinetic outcomes for diazepam in a younger man (A) and an older man (B) ). In fact, physiologic changes with aging affect many aspects of pharmacokinetics (see Pharmacokinetics in Older Adults Pharmacokinetics in Older Adults Pharmacokinetics is best defined as what the body does to the drug; it includes Absorption Distribution across body compartments Metabolism Excretion read more and Pharmacokinetics in Children Pharmacokinetics in Children Pharmacokinetics refers to the processes of drug absorption, distribution, metabolism, and elimination. There are important age-related variations in pharmacokinetics. Absorption from the gastrointestinal... read more ).
Other factors are related to individual physiology. The effects of some individual factors (eg, renal failure, obesity, hepatic failure, dehydration) can be reasonably predicted, but other factors are idiosyncratic and thus have unpredictable effects. Because of individual differences, drug administration must be based on each patient’s needs—traditionally, by empirically adjusting dosage until the therapeutic objective is met. This approach is frequently inadequate because it can delay optimal response or result in adverse effects.
Knowledge of pharmacokinetic principles helps prescribers adjust dosage more accurately and rapidly. Application of pharmacokinetic principles to individualize pharmacotherapy is termed therapeutic drug monitoring.
Clinical pharmacology is the study of the interactions between drugs and the human body. Pharmacokinetics and pharmacodynamics are two broad divisions within clinical pharmacology. The complex, biochemical interactions that occur between the body’s natural processes and the chemical composition of a pharmaceutical drug are measured and described by pharmacokinetics and pharmacodynamics which both play a pivotal role in determining a drug’s safety and efficacy. Regulatory agencies, such as the FDA, are responsible for approving new drugs or deciding whether or not a drug should be taken off the market. Regulatory agencies are also responsible for ensuring that all available drugs are effective and safe for human use. Understanding the safety and effectiveness of any drug depends, in part, on pharmacokinetics and pharmacodynamics. Pharmacokinetics vs. PharmacodynamicsThe main difference between pharmacokinetics and pharmacodynamics is that pharmacokinetics (PK) is defined as the movement of drugs through the body, whereas pharmacodynamics (PD) is defined as the body’s biological response to drugs. In other words, PK describes a drug’s absorption, distribution, metabolism, and excretion (also known as ADME) and PD describes how biological processes in the body respond to or are impacted by a drug. Put in the simplest terms, pharmacokinetics is what the body does to the drug and pharmacodynamics is what the drug does to the body. While PK describes a drug’s exposure by characterizing its ADME properties and bioavailability as a function of time, PD describes a drug’s response in terms of biochemical or molecular interactions. PK/PD together can be thought of as an exposure/response relationship. Understanding the exposure-response relationship (PK/PD) is key to the development and approval of every drug. PK and PD data contribute to about 25% of what is in a drug package insert or drug label. Strategic planning of the overall drug development program and an intelligent pharmacokinetic study design can accelerate the development process to help ensure safety and efficacy endpoints are achievable. The Importance of Pharmacokinetic and Pharmacodynamic AnalysesPK and PD analyses are important because they help us understand how drugs behave in the body and how the body reacts to drugs, respectively. Drug developers use insights gained from PK and PD analyses to design better clinical studies (i.e., what dose to use or how different drugs interact with each other in the body). Clinicians use the information from PK and PD analyses (as presented in the drug label or package insert) to treat different types of patients (e.g., patients with and without renal impairment or elderly versus younger patients). How to Use Pharmacokinetic and Pharmacodynamic AnalysesPK and PD analyses can be used to determine a number of important drug development parameters related to clinical study design. PK and PD analyses can be used to:
Pharmacokinetics and Pharmacodynamics ServicesOur PK and PD services include:
PK/PD Analysis and Reporting
Designing and Interpreting Pre-clinical ADME and Clinical Studies
Dosing SimulationsOnce a model has been constructed, different dosing regimens can be simulated to predict exposure. This type of service can save valuable time and resources when trying to design and justify dosing regimens in clinical studies Risk AnalysisBy integrating PK/PD models with pre-clinical data, probabilistic risk analysis can make drug development more efficient by eliminating candidates with a high risk of failure in clinical trials. Integrated PK Study Reports or Standalone PK ReportsEnsuring that a study report conveys the appropriate information to health authorities requires subtle messaging and a rigorous attention to detail. Data Management and CDISC Dataset GenerationIn addition to storage and security, considerations regarding data collection and interrogation should be made at the beginning of a study to maximize the utility of a dataset after it is locked. Read more about our data management services here. All clinical data submitted to health authorities must conform to the Clinical Data Interchange Standards Consortium (CDISC) format. Our data managers specialize in this type of reporting and are extremely efficient at CDISC conversion. Contact our PK/PD Experts for GuidanceNuventra is a leading PK/PD science consulting group in terms of our expertise and customer service. We provide exceptional clinical & nonclinical noncompartmental PK analyses to support drug development programs. Our flexible reporting options range from simple outputs to robust submission-ready pharmacokinetic reports. Contact us today to learn more about how our variety of PK analyses services can benefit your program. We enjoy working closely with our clients to determine the most appropriate and cost-effective options for each unique drug development program. Contact Us |