Clinical Pharmacology

Introduction

Clinical pharmacology has been defined as "that discipline that teaches, does research, frames policy, gives information and advice about the actions and proper uses of medicines in humans and implements that knowledge in clinical practice". Clinical pharmacology, in theory, has been practiced for centuries through observing the effects of herbal remedies and early drugs on humans. Today, clinical pharmacology has expanded to be a multidisciplinary field and has contributed to the understanding of drug interaction, therapeutic efficacy and safety in humans. Stable isotope technology based on stable isotope-labeled products has been applied in clinical pharmacology since 1972. It is considered as a technology with proven and promising value, depending on the area of application in the field of clinical pharmacology.

Safety

At present, the stable isotope-labeled products commonly used in clinical pharmacology studies are ²H, ¹³C, ¹⁵N, ¹⁸O labeled substances. According to existing research reports, the toxicity related to the isotope effect of deuterium can only be produced by very high levels of deuteration (>15% of body water), which greatly exceeds the amount of deuterium given in a typical tracer dose of drug. ¹⁸O by inhalation and orally (incorporated in drinking water) to mice and found no biological effect. And administration of ¹³C-labeled endogenous substances, such as carbohydrates and lipids never induced intoxication, either when administered as a single oral dose or as a continuous intravenous infusion. It can be concluded that application of stable isotope-labeled substances at historically applied enrichment levels has proved not to pose any clinically relevant risk.

Applications

There are three main aspects of application of stable isotope technology based on labeled products in clinical pharmacology, including assessment of drug pharmacology, assessment of drug products or drug delivery systems and assessment of patients ^[1].

Assessment of drug pharmacology: Stable isotope technology based on stable isotope-labeled substances is applied in the assessment of drug pharmacology can be used to determine the pharmacokinetic profile, action mechanism of a drug substance and the mechanism of toxicity and adverse effects. For example, how carbidopa, a dopa-decarboxylase inhibitor, affects peripheral levodopa pharmacokinetics was investigated by using 1,2,3,4,5,6-¹³C levodopa as the drug substance. And to show the action mechanism of fibrates in vivo in humans, ¹³C-Valine or another labeled amino acids were used.

Assessment of drug products or drug delivery systems: In this aspect, stable isotopes can be used to determination of bioavailability (include absolute bioavailability and elative bioavailability) and release profile of drug delivery systems. For example, the absolute bioavailability of oral N-acetylprocainamide was determined by comparing its kinetics with that of co-administered ¹³C-N-acetylprocainamide by intravenous injection. More examples are shown in Table 1 ^[1].

Table.1 The application of stable isotope technology to assess the bioavailability or release profile of drug products and delivery systems

Abbreviations: ABA, absolute bioavailability; RBA, relative bioavailability; and RP, release profile.

Assessment of patients: In this aspect, phenotyping, monitoring drug treatment effect and clinical toxicology can be determined. The ¹³C-urea breath test is applied to monitor drug treatment efficacy and the ¹³C-methacetin, ¹³C-caffeine or ¹³C-galactose breath tests can be used to assess the clinical toxicology of drug substances.

What can we do?

Alfa Chemistry has many years of experience in the synthesis and development of stable isotope-labeled products. We can provide various stable isotope-labeled compounds for clinical pharmacology research, including stable isotope-labeled drug precursors, carbohydrates, lipids and many others. And our professional technology teams that can also provide customers with high-quality stable isotope-labeled compounds design and customization services. No matter what design ideas you have, we will implement them together with you. Please contact us immediately to order or cooperate in research and development with high quality and reasonable price.

Reference

• Schellekens, R. C. A., et al. Applications of stable isotopes in clinical pharmacology[J]. British journal of clinical pharmacology, 2011, 72(6): 879-897.