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-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.
Ready To Get Started?
Complete the Form below to schedule a Discovery Call with a member of our medical team to learn how BioPharma Services can be your trusted Bioequivalence partner!
Schedule a Discovery Call
Learn how BioPharma Services can be your trusted clinical trial partner.