Introduction

Drug interaction can alter the pharmacokinetics and/or pharmacodynamics of a drug. In pharmacokinetic drug interactions, the concentrations of one or more drugs are altered by another drug. This change in concentration in a given drug may be due to changes in absorption, distribution, metabolism, or elimination (1). The pharmacodynamic drug interactions can be either negative (toxic effects) or positive (therapeutic benefit) and may be due to various mechanisms including receptor interaction and changes in effector mechanisms (1). For example, the combination therapy of ribavirin and interferon (IFN)-a2b in patients with chronic hepatitis C provided improved therapeutic benefit than either treatment alone, and the safety profiles of combination therapy were similar to the monotherapy treatment (2).

Biological products such as therapeutic proteins and monoclonal antibodies are becoming widely popular for the management and cure of many diseases. These products are termed as macromolecules because of their size (>1000 Da). Therapeutic proteins are naturally occurring substances in the body, each having a unique amino acid sequence and thus distinct physicochemical properties. These differences in properties affect the folding, formulation, and stability of each protein. Indeed, long-term stability issues associated with many protein therapeutics can pose unique challenges for pharmacokinetic studies. Administration of exogenous proteins can influence the stimulation or feedback mechanism of endogenous proteins, thus estimation of pharmacokinetic parameters may become difficult (3).

To properly understand the mechanism of interaction of therapeutic proteins or monoclonal antibodies with other drugs (small as well as macro-molecules), it is important to know the pharmacokinetic characteristics (especially metabolism and elimination) of these macromolecules.

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