Preclinical drug metabolism and pharmacokinetics (DMPK) studies are essential for characterizing drug absorption, distribution, metabolism, and excretion (ADME), as well as for identifying potential drug-drug interactions, optimizing dosage regimens, and supporting clinical trial design. Non-human primates (NHPs) are widely used in DMPK research because of their genetic, physiological, and pathological similarities to humans. However, microbial infections in NHPs can alter immune status, hematological parameters, biochemical markers, organ function, and stress responses, thereby confounding pharmacokinetic interpretation. Therefore, rigorous microbial screening, quarantine, and health monitoring are critical to ensuring the reliability and reproducibility of DMPK study results.
Mycobacterium tuberculosis (TB) is one of the most important zoonotic pathogens in NHP colonies and is mainly transmitted through respiratory droplets, aerosols, contaminated secretions, feed, or water. Infected monkeys may show decreased appetite, weight loss, progressive emaciation, respiratory distress, lethargy, and abnormal radiographic findings such as bronchopneumonia. Acute infections may progress rapidly with few obvious clinical signs, while chronic or progressive cases can involve hepatosplenomegaly, lymph node enlargement, ulceration, and disseminated nodular lesions with caseous necrosis. Because TB infection in NHPs can resemble human disease and poses significant risks to both animal colonies and personnel, strict quarantine, regular screening, and isolation of infected animals are essential.
Cercopithecine Herpesvirus 1, also known as B virus, naturally infects macaques and often remains asymptomatic, although some animals may develop oral or genital ulcers. The virus is present in saliva, blood, and other body fluids and can cause subtle physiological and biochemical changes in infected NHPs. For example, seropositive cynomolgus macaques may show altered liver-related markers such as ALT, AST, and total bilirubin, as well as changes in white blood cell, hemoglobin, and monocyte levels. These subclinical abnormalities may influence ADME processes and interfere with DMPK data interpretation. In humans, B virus infection is rare but can cause severe neurological disease and high mortality if untreated, making continuous monitoring and preventive biosafety measures necessary.
Enteric pathogens such as Salmonella spp. and Shigella spp. are also important in NHP management because they are transmitted mainly through the fecal-oral route and can cause diarrhea, bloody or mucoid stools, abdominal pain, fever, and appetite loss. Shigella infections are relatively common in NHPs, and animals may carry these pathogens without symptoms until stressors such as transportation, quarantine, or breeding trigger disease. Although infections can often be controlled with antibiotics and confirmed through post-treatment testing, preventive management remains essential, including regular screening, improved hygiene, stress reduction, and strict quarantine procedures. These pathogens are also zoonotic, so biosafety controls are needed to protect laboratory personnel from gastrointestinal infection.
In addition to required zoonotic pathogen exclusion, retroviruses such as Simian Immunodeficiency Virus (SIV), Simian Retrovirus (SRV), and Simian T-lymphotropic Virus (STLV) require close attention because they can establish persistent infections and alter physiological or immune parameters. SIV can cause immunodeficiency-like disease, chronic diarrhea, weight loss, opportunistic infections, and hematological or biochemical abnormalities. SRV may suppress T- and B-cell function, cause anemia or granulocytopenia, and has been reported to compromise the validity of NHP studies. STLV primarily affects lymphocytes and may alter cytokine expression, immune responsiveness, and susceptibility to other pathogens. For this reason, high-quality DMPK programs often use "five-negative" NHPs that are negative for TB, B virus, SIV, SRV, and STLV, supported by source audits, arrival quarantine, microbial testing, complete blood counts, serum biochemistry, routine health checks, pre-study screening, veterinary evaluation, adequate washout periods, and positive reinforcement training to reduce procedural stress during restraint and blood collection.
Conclusion
Preclinical DMPK studies play a pivotal role in innovative drug development. NHPs, as a critical animal model, have their health and quality directly impacting the reliability and reproducibility of research results. Prisys Biotech consistently upholds high-quality industry standards for NHPs. The NHPs used in our DMPK studies are all "five-negative monkeys," providing a solid guarantee for the reliability of experimental results. Moreover, through our unique restraint and blood collection training methods, we can effectively reduce stress responses in NHPs, ensuring the accuracy and reproducibility of experimental outcomes, thereby better facilitating innovative drug research and accelerating the drug development and market launch process.
