Pharmacokinetics Studies
Pharmacokinetics (PK) investigates the interactions of an administered substance with the body from its administration until its excretion. In clinical drug development, PK studies focus on New Chemical Entities (NCEs) or New Investigational Medicinal Products (IMPs).
Pharmacokinetic studies are a key component of clinical drug development, and their findings are required for submission of registration files to regulatory authorities. However, the design and conduct of pharmacokinetics may be complex and challenging. They need the expertise of a multidisciplinary team, including pharmacokinetic scientists, physicians, bioanalytical scientists, and biostatisticians, as well as access to state-of-the-art clinical and bioanalytical facilities. In line with this idea, a study that analyzed published reports of pharmacokinetic studies conducted in the context of Phase 1 clinical trials found that pharmacokinetic data were often not reported or incomplete.
What are Pharmacokinetic Studies in Clinical Trials?
Pharmacokinetics are performed as a part of clinical trials, to investigate the absorption, distribution (including protein-binding data), metabolism, and excretion (including interindividual variability) of NCEs. The pharmacokinetic parameters of a drug can be evaluated by analyzing blood or urine samples collected at various time points after drug administration. The samples should be collected and handled according to standardized procedures to minimize variability and ensure accuracy.
Based on the acquired pharmacokinetic data, the peak NCE concentration (Cmax), steady-state concentration (Css), trough concentration (Ctrough), time to reach the peak (Tmax), area under the concentration/time curve (AUC), volume of distribution, half-life, and clearance (CL) are calculated. The sampling frequency is also planned carefully to ensure that a sufficient number of time-points are analyzed.
Pharmacokinetics also determine the dosage and dosage intervals for administering NCEs. Single-dose and multiple-dose pharmacokinetic studies can be conducted. In multiple ascending dose studies, it is recommended to select a study duration that enables establishing the steady-state concentrations of NCEs, their dose dependence, and variability.
In addition, pharmacokinetic data can be used in pharmacokinetic/pharmacodynamic modeling to help understand the relationship between exposure to an NCE and its response. If adverse reactions due to drug interactions are suspected, drug interaction studies should be conducted. Further, if there are concerns that food may affect the absorption of an NCE, a food-effect study should also be performed.
Integration of Pharmacokinetic & Other Clinical Data
Pharmacokinetic data can be used in pharmacokinetic/pharmacodynamic modeling to help understand the relationship between exposure to an NCE and the response to it. Pharmacokinetic/pharmacodynamic modeling is an exploratory analysis that is based on mathematical and statistical models and that can facilitate all stages of drug development. For example, it can help optimize clinical trial design, select a dose and regimen for further testing, and predict the response of certain subpopulations or the existence of drug-drug interactions. Pharmacokinetic/pharmacodynamic modeling can accelerate “go or no-go” decisions by helping elucidate the pharmacokinetic and pharmacodynamic properties of an NCE and their relationship with each other
If adverse reactions due to drug interactions are suspected, drug-drug interaction studies should be conducted. However, pharmacokinetic/pharmacodynamic modeling may also help unmask such relationships and elucidate their importance, thus potentially reducing the extent of required drug-drug interaction studies. Further, if there are concerns that food may affect the rate of absorption of an NCE, a food-effect study should also be performed.
Preclinical Data
When designing clinical trials, including studies of pharmacokinetics, the preclinical dataset of a drug development program may provide important information that can facilitate the clinical trial design. Preclinical data may help predict how likely it is to achieve therapeutic exposure during an early-phase clinical trial using a particular dosing regimen.
It has been demonstrated that applying best practices for the generation of experimental data using advanced predictive methodologies — and thoroughly mechanistically understanding the disposition properties of an NCE prior to its selection for clinical development — may maximize the likelihood of successfully predicting its pharmacokinetics. Nevertheless, since animal models do not fully encompass the characteristics of a medical condition, it remains challenging to extrapolate preclinical data to humans.
Goals of Pharmacokinetic Studies
The overall the aim of pharmacokinetics is to determine the following:
- Safe and effective dose range and dosing regimen of an NCE
- Appropriate route and frequency of its administration
- Duration of treatment required for sustained therapeutic effects
- Assess food effects
- Evaluate gender, age profile differences
- Assess any difference in PK profile with renal or hepatic patients for potential dose adjustment
This is important for the efficacious and safe administration of NCEs, the development of appropriate therapeutic schedules, and potential dose adjustments. Drug candidates with a narrow therapeutic range require particular attention in terms of elucidating their pharmacokinetics due to an increased toxicity risk.
Dr. John Oldenhof, MSc, PhD, Chief Scientific Officer
18 years of experience having overseen 250+ early phase and HAP and Abuse Liability Studies
Expert Full-Service Solutions for Your Pharmacokinetic Studies
BioPharma Services, Inc. is a full-service clinical research organization (CRO) that offers comprehensive solutions for our clients’ clinical trial programs and has niche expertise in early-phase clinical trials. Our multidisciplinary, award-winning team and modern facilities enable us to competently address all requirements of our clients’ clinical trials, including their pharmacokinetic studies.
A Dedicated Team of Proficient Pharmacokinetic Scientists
Our pharmacokinetic scientists have generated thousands of study designs to support drug submissions to multiple regulatory markets across the globe. The team is also responsible for developing innovative design solutions for all drug programs, from generic equivalents to new drug candidates. It is led by BioPharma’s chief scientific officer (CSO), Dr. John Oldenhof, a widely recognized expert in the field of clinical pharmacology.
Expert Medical Physicians
All pharmacokinetic study designs, clinical trials, and clinical drug development plans at BioPharma are supported by our panel of expert medical physicians that ensure foremost that the safety and well-being of our study volunteers are the highest priority. Whether the strategy is to dose a generic drug equivalent in healthy volunteers versus a patient panel or to proceed with a new drug candidate, our physician team’s primary objective is to maintain the health and welfare of our subjects, with ethical and safety considerations driving their decisions.
State-of-the-art Clinical Facilities
BioPharma has established two clinical research centers that enable us to plan and conduct various early-phase clinical trials, including pharmacokinetic studies. Our clinical research centers are equipped with participant safety as the utmost priority and are operated by a highly qualified team of healthcare professionals.
An in-house Bioanalytical Laboratory
Bioanalytical techniques are essential for determining the concentrations of NCEs and their metabolites. BioPharma’s in-house laboratory is equipped with an innovative liquid chromatography with a tandem mass spectrometry (LC/MS/MS) platform. All assays are performed by our in-house team of efficient and experienced bioanalytical scientists. To address the diverse needs of our clients’ clinical drug development programs, they have fully validated over 230 bioanalytical assays.
Integration of Pharmacokinetic Data with Other Clinical Trial Results
Relating findings of pharmacokinetics to efficacy and toxicity can provide deeper insight into the clinical development of NCEs. BioPharma’s multidisciplinary team enables us to efficiently perform data integration in order to streamline the drug development process.
Access to an Extensive Database of Study Volunteers
Patient-related factors, such as age, sex, genetic factors, obesity, renal and hepatic function, and smoking and drinking patterns may influence drug pharmacokinetics. BioPharma Services has created a large database with over 18,000 potential study participants, including normal healthy volunteers (NHVs) and special populations.
Experience with Various Formulations and Routes of Administration
The pharmacokinetic properties of NCEs can also be influenced by their formulation and route of administration. BioPharma has expertise in working with a variety of drug formulations. In addition, we can employ even challenging routes of administration due to the proficiency of our internal team and network of external collaborators.
A Team of Expert Biostatisticians
BioPharma biostatisticians support the statistical plan and analysis of all clinical studies that we conduct, including pharmacokinetics. They have experience with modeling and simulation tools that greatly enhance the analysis of pharmacokinetic studies.
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Pharmacokinetics FAQ
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In Pharmacokinetics, What Are the 4 Stages of Drug’s Journey in Body?
Pharmacokinetics refers to the study of how the body interacts with a drug. The four stages in body are Absorption, Distribution, Metabolism, and Excretion (ADME). Absorption refers to how the drug is taken into the body, whether through ingestion, inhalation, injection, or other means. Distribution refers to how the drug is transported through the body’s bloodstream to its target site of action. Metabolism refers to how the drug is broken down and transformed into other substances in the body. Excretion refers to how the body eliminates the drug and its metabolites from the body.
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What is a Pharmacokinetic Study in Clinical Trials?
A Pharmacokinetic study or study with PK endpoints aims to measure the way a drug is absorbed, distributed, metabolized, and excreted in the body. Pharmacokinetic studies are essential for understanding how different a drug formulation and body’s physiology affect its pharmacokinetics. These studies involve administering the drug to a group of study participants and measuring drug levels in their blood or other bodily fluids over time.
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What Are 4 Factors That Affect Absorption of a Drug?
There are several factors that can affect the absorption of a drug in the body. Four of the most significant factors include:
- Route of administration: Different routes of administration, such as oral, intravenous, or topical, can affect how quickly and effectively a drug is absorbed into the body.
- Solubility: The solubility of a drug in various body fluids can affect how quickly and effectively it is absorbed.
- pH: The pH of the body fluid where the drug is administered can also affect absorption, as some drugs are better absorbed in acidic environments, while others are better absorbed in basic environments.
- Presence of food or other drugs: The presence of food or other drugs in the body can affect the way a drug is absorbed, as they may interfere with the drug’s absorption or metabolism.
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What Are the Regulatory Requirements for Pharmacokinetics Studies?
The regulatory requirements for pharmacokinetics studies in Canada and the United States are outlined by Health Canada and the Food and Drug Administration (FDA), respectively. In Canada, According to Health Canada’s guidelines, PK studies should be conducted in all phases of clinical trials to support the safety and efficacy of the drug. The Pharmacokinetics data collected should be used to determine the appropriate dose, dosing frequency, and/or duration of therapy. Similarly, in the United States, the FDA requires Pharmacokinetics studies to be conducted to support the safety and efficacy of a drug. Pharmacokinetics data is used to assess the relationship between the drug concentration at the site of action and the therapeutic effect. The FDA recommends that PK studies be conducted in all phases of clinical trials, with a focus on understanding the ADME of the drug and the impact of intrinsic and extrinsic factors on drug exposure.
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How Long Does it Typically Take to Conduct a Pharmacokinetics Study?
There is no typical duration for a PK study which varies depending on several factors, such as the type and purpose of the study, the number of participants, the drug being tested, and the regulatory requirements.
- Generally, a single-dose, 2 way-crossover, pharmacokinetics study with a few healthy volunteers can take around 2–4 weeks for the study to conduct depending on the washout duration between periods.
- Multiple-dose pharmacokinetics studies can take longer, usually around 2–6 weeks, as the participants need to be administered with the drug for several days or weeks to observe the drug’s accumulation and steady-state pharmacokinetics. Using a washout or direct switch can impact the duration of the study conduct.
- Complex pharmacokinetics studies, such as drug-drug interaction studies or special populations studies, or study when the primary end points are long-term safety or efficacy can take several months or even years to complete.
It’s important to note that the timeline for a pharmacokinetics study can also be affected by various factors, such as the PK characteristic of the drug, availability of participants, the complexity of the study design, the occurrence of adverse events, and the regulatory review process.