A Qualitative Review on the Pharmacokinetics of Antibiotics in Saliva: Implications on Clinical Pharmacokinetic Monitoring in Humans

Abstract

We conducted a systematic search to describe the current state of knowledge regarding the utility of saliva for clinical pharmacokinetic monitoring (CPM) of antibiotics. Although the majority of identified studies lacked sufficient pharmacokinetic data needed to assign an appropriate suitability classification, most aminoglycosides, fluoroquinolones, macrolides, penicillins/cephalosporins, and tetracyclines are likely not suitable for CPM in saliva. No clear pattern of correlation was observed between physiochemical properties that favor drug distribution into saliva and the likelihood of the antibiotic being classified as suitable for CPM in saliva (and vice versa). Insufficient data were available to determine if pathophysiological conditions affected salivary distribution of antibiotics. Additional confirmatory data are required for drugs (especially in patients) that are deemed likely suitable for CPM in saliva because only a few studies were available and many focused only on healthy subjects. All studies identified had relatively small sample sizes and exhibited large variability. Very few studies reported salivary collection parameters (e.g., salivary flow, pH) that could potentially have some impact on drug distribution into saliva. The available data are heavily weighted on healthy subjects, and insufficient data were available to determine if pathophysiology had effects on saliva drug distribution. Some studies also lacked assay sensitivity for detecting antibiotics in saliva. Overall, this review can be useful to clinicians who desire an overview on the suitability of saliva for conducting CPM of specific antibiotics, or for researchers who wish to fill the identified knowledge gaps to move the science of salivary CPM further.

Pharmacokinetic considerations regarding the treatment of bacterial sexually transmitted infections with azithromycin: a review

“…For example, only free drug or low molecular weight drugs can distribute into saliva which may or may not have an impact on treatment efficacy for oropharyngeal STIs. 42 There is also evidence that the MIC of a drug can vary by infection site with a recent study finding that the CT MIC for azithromycin was about four times higher in a colorectal compared to an endocervical cell line, regardless of CT genovar. 43 For STIs, it is essential that the antimicrobial used effectively distributes to all possible infection sites including oropharyngeal, anorectal or urogenital sites.…”

“…The pharmacokinetics of antimicrobials in the pharyngeal mucosa is complex and it is not clear what relative antimicrobial concentrations are required in tissue and saliva to cure oropharyngeal STIs, or even whether saliva concentrations are needed at all. 42 Further, little is known about the microbiology of STIs in the oropharynx. Take NG as an example.…”

Antibiotic PK/PD Research in Critically Ill Neonates and Children: How do we Proceed?

“…Although, this approach has been studied for therapeutic drug monitoring of specific antibiotics in (healthy) adults, and to a limited extent in children, data are often insufficient to evaluate the suitability. Cross-validation between the standard (plasma) and alternative matrix are needed [15].…”

Membrane Filtration Is Suitable for Reliable Elimination of Mycobacterium tuberculosis from Saliva for Therapeutic Drug Monitoring

“…Therapeutic drug monitoring (TDM) of blood could be helpful in optimizing TB treatment, as anti-TB drug exposure shows interpatient variability (1). TDM in saliva instead of blood is currently being studied as a more practical alternative, since saliva sampling is noninvasive and more acceptable to patients (2,3). Along with the growing interest in the pharmacokinetics of anti-TB drugs, TDM is increasingly used in daily routine practice.…”