Drug Concentrations In Saliva Research Articles

An exploratory study of drug concentration and inhibitory effect of cetylpyridinium chloride buccal tablets on SARS-CoV-2 infection among 10 Chinese subjects.

It was evidenced that cetylpyridinium-chloride (CPC) mouthwash could inhibit SARS-COV-2 activity and reduce salivary viral load, thus reducing SARS-CoV-2 transmission. However, due to insufficient residence time in the oral cavity, CPC-containing mouthwashes have no prolonged antiviral effect. The duration of action of the CPC buccal tablet is expected to be longer than that of the mouthwash. However, there are currently no reports on the salivary drug concentration of CPC buccal tablets. The study aimed to investigate the salivary drug concentration of CPC buccal tablets and the antiviral effect of CPC on SARS-CoV-2 in vitro. This is a single-dose, single-arm clinical trial, involving 10 Chinese healthy subjects who received 2-mg CPC buccal tablet to collect saliva samples and to detect saliva concentration at different timepoints within 2h (Clinical Trial Registration Number: NCT05802628, Registration Date: April 6, 2023). CPC concentration in saliva was detected by liquid chromatography tandem mass spectrometry (LC-MS/MS), and pharmacokinetic parameters were calculated based on the non-compartmental model. With an in vitro antiviral experiment, the activity of CPC buccal tablets against SARS-CoV-2 and its cellular toxicity was tested. Drug concentrations in saliva at 15 min, 30 min, 1h, 1.5h, and 2h after administration were 8008.33 (1042.25, 41081.11), 2093.34 (373.15, 5759.83), 1016.58 (378.66, 3480.68), 891.77 (375.66, 6322.07), and 717.43 (197.87, 2152.71)ng/mL. PK parameters of saliva concentration: Cmax = 8008.33 (1042.25, 41081.11)ng/mL, AUC0-t = 4172.37 (904.42, 13912.61)ng/mL*h, AUC0-∞ = 6712.85 (1856.77, 19971.12)ng/mL*h, T1/2 = 1.22 (0.59, 2.83)h, Tmax = 0.25 (0.25, 0.25)h. As determined in in vitro experiment, CPC was active on SARS-CoV-2 with cytotoxic and inhibitory activity of CC50 = 35.75 μM (≈12155 ng/mL) and EC50 = 7.39 μM (≈2512.6ng/mL). The comparison between the salivary CPC concentration and EC50/CC50 values from in vitro antiviral experiments suggests that CPC buccal tablets may inhibit SARS-CoV-2 activity, and the inhibition may last for approximately 30 min without cytotoxicity.

Spitting for Science: Non-Invasive Drug Monitoring Through a Modified Liquid Micro Junction-Surface Sampling Probe

The use of saliva as a convenient, non-invasive alternative for therapeutic drug monitoring has become increasingly favorable with the emergence of pharmacokinetic and bioequivalence research providing a link between blood plasma and saliva concentrations. Therapeutic drug monitoring is a practice through which specific drugs are monitored at given time intervals to maintain a constant concentration in the blood. It is only necessary for patients taking drugs with known pharmacokinetic variability, narrow therapeutic indices and potential adverse effects.
 Although the drug concentration in saliva is lower than in plasma, saliva has a complex matrix, consisting of salts, immunoglobins, proteins and more. The polar matrix in the saliva introduces potential interference with the sensitivity of the drug detection through salt suppression.
 In this project, 6 drugs used as anticonvulsants and antidepressants were analysed in artificial saliva using a modified version of the Liquid Micro Junction-Surface Sampling Probe (LMJ-SSP) to maximize the sensitivity of observed signals and minimize the detection limits.
 The main parameter which was targeted for optimizing the extraction and ionization of the drug in the saliva samples was the polarity of the carrier liquid, which continuously flows in the coaxial tube of the LMJ-SSP. Upon analyzing four different carrier liquids, the mixture containing methanol, water and chloroform was determined to provide the best sensitivity. Additionally, the enrichment factors of the peak areas using the chloroform mixture in the modified LMJ-SSP were enhanced by a factor ranging between 2.9 to 31.4, depending on the analyte.
 Overall, the data obtained from this project thus far displays that modifying the polarity by modifying the carrier liquid composition to balance the extraction and ionization during analysis using the modified LMJ-SSP optimizes the sensitivity of the detection.

Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma.

Therapeutic drug monitoring (TDM) is used in certain clinically selected cases and in research settings to optimize the response to antiretroviral therapy. Plasma of blood is commonly used for TDM, but blood sampling is invasive and at risk for transmission of infectious agents. On the other hand, saliva sampling is noninvasive, safe, cheap, and easily performed compared to blood. Dolutegravir (DTG) is now widely prescribed as a key component of antiretroviral therapy for HIV infection. In this study, we examined the relationship between DTG concentrations in plasma and saliva of treated patients to explore the possibility of using saliva as an alternative body fluid of TDM. A total of 17 pairs of blood and saliva samples were obtained from 15 consented HIV-1-infected subjects treated with DTG containing regimens for more than one month. Both blood and saliva samples were collected within 1 h of each other. Drug concentrations were determined by liquid chromatography-tandem mass spectrometry using DTG-d5 as an internal standard. The LLOQ was 0.5 ng/mL. The calibration curves were prepared with pooled plasma or saliva containing DTG in a range of 0.5–100 ng/mL with precision of <14.4% and accuracy within ±14.7%. The DTG concentrations in the plasma and saliva were significantly correlated (Pearson’s correlation coefficient r = 0.76, p < 0.001). The median ratio of the drug concentration in saliva to those in plasma was 0.0056, which is close to the rate of non-protein-bound DTG in plasma (0.70%), suggesting that only free DTG in plasma is transported to the salivary glands and secreted into saliva. The present study demonstrates that DTG concentration in saliva reflects the pharmacologically active drug concentration in plasma and may provide an easily accessible alternative for monitoring effective antiretroviral treatment.

A Simple Electrochemical Swab Assay for the Rapid Quantification of Clonazepam in Unprocessed Saliva Enabled by Lubricin Antifouling Coatings

AbstractThe electrochemical sensing of clonazepam in samples of unprocessed saliva is reported, using commercially available reduced graphene oxide (rGO) screen printed electrodes (SPEs). The rGO electrodes were modified with self‐assembled lubricin (LUB) antiadhesive coatings that function as a size‐selective molecular sieve that partitions small molecule analytes from large fouling molecules at the electrode‐fluid interface. By mitigating the adverse effects of protein fouling, these LUB coatings enable direct, reliable, and quantitative electrochemical measurements of clonazepam concentrations in untreated saliva, which was not possible with uncoated rGO electrodes in identical tests. The proposed assay design, which is suitable for disposable point‐of‐care diagnostics requires no sample pre‐treatment and shows a linear detection response over a concentration range of 25–250 nM with a correlation coefficient of R2=0.987 and a limit of detection (LoD) of 16.67 nM. The swab‐based sample acquisition method paired with the antifouling properties of the LUB coatings provide a cost effective and practical biosensing platform for assessing electroactive drug concentrations in saliva in a point‐of‐care setting.

Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.

Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer. The strongest risk factors were found in the AA genotype and allele of SNP rs3892097 from the CYP2D6 gene, followed by the alleles A and T of SNPs rs2740574 and rs2687116, respectively from CYP3A4. The most important concomitance was between homozygous genotype AA of rs3892097 and genotype AA of rs2740574 with 78.3% in drug-resistant epilepsy patients as compared to 14.3% in control patients. The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing drug resistance and CYP2D6, CYP2C19 SNPs and haplotypes may affect the response to antiepileptic drugs.

Saliva concentration of amoxicillin, erythromycin, and ciprofloxacin in outpatients: a comparison between the young and the elderly

Saliva is a still poorly investigated specimen concerning issues of antibiotic diffusion. The knowledge of antimicrobial drug concentrations in saliva, following systemic drug administration, may h...

Interpretation of oxycodone concentrations in oral fluid

The purpose of this retrospective study was to compare oxycodone concentrations in saliva and whole blood with a view to propose therapeutic concentrations in oral fluid. Oral fluid is an easy specimen to collect with several advantages over urine, including ease of collection and difficulty of adulteration. As oral fluid is a reflection of free drug circulating in the blood, drug concentrations in saliva are more closely related to blood levels than urine concentrations. The number of testing laboratories offering the analysis of prescription pain medications in urine has increased significantly over the last few years, along with the overuse and abuse of pain killing drugs, specifically oxycodone. Hence, the utility of oral fluid analysis in this field was assessed. Paired specimens of blood and oral fluid were retrospectively studied in an attempt to establish a range for oxycodone concentrations in oral fluid reflective of therapeutic intake. Twenty-three paired oral fluid-blood specimens were studied. Oral fluid samples had been collected with the Quantisal™ oral fluid device, stored cold and shipped overnight to the laboratory prior to testing. Blood specimens were collected simultaneously in gray top tubes. From 23 pairs of samples, the median concentration in oral fluid was 524 μg/L and blood was 53 μg/L. The whole blood to plasma ratio for oxycodone was 1.3, so the median plasma concentration was 41 μg/L projecting a saliva to plasma ratio (S:P ratio) of 12. The comparison of oral fluid-blood concentrations allowed the projection of a S:P ratio for oxycodone and the development of a potential therapeutic range for oxycodone in oral fluid. Saliva drug concentrations in pain management are more closely related to blood levels than urine so can be more easily interpreted. These data provide a foundation for interpretative advances; however, further research surrounding other pain medications and controlled studies are necessary.

Determination of the salivary retention of hexetidine in-vivo by high-performance liquid chromatography.

The non-antibiotic antimicrobial agent hexetidine is widely used at a concentration of 0.1% w/v as an oral rinse to reduce the number of viable microorganisms within the oral cavity. However, following use, the available concentration of hexetidine in the oral cavity declines with time, thus compromising the resultant antimicrobial activity. It is, therefore, desirable to determine the persistence of the agent in the oral cavity by quantification of the drug concentration in saliva, thus enabling prediction of its antimicrobial activity in the oral environment. A rapid reverse-phase HPLC method was therefore developed and validated for hexetidine in aqueous solution (Oraldene) and in saliva samples collected from volunteers post-rinsing with 15 mL of hexetidine oral rinse for 30s. The HPLC assay was sufficiently sensitive to accurately detect hexetidine in saliva up to 25 min after in-vivo use of a commercial oral rinse. Furthermore, it was possible to detect hexetidine below the published minimum inhibitory concentrations (MICs) for a selection of microorganisms. From these data a first-order elimination rate constant of hexetidine from the oral cavity was determined post-rinsing in each of six volunteers. The validated HPLC assay method presented is useful for the assay of hexetidine in the oral cavity both at and below MICs. The first-order elimination rate constant shows significant variation between volunteers.

The Use of Oral Fluid for Therapeutic Drug Management

One of the underlying tenets of clinical pharmacology is that only free drugs are pharmacologically active. It is thought that only free drugs can cross biological membranes to interact with a given receptor to alter its function, and that drug responses, both efficacious and toxic, are a function of unbound concentrations. The rationale for measuring drugs in oral fluid is that the free fraction of a drug in plasma reaches equilibrium with the drug in saliva. Although reports concerning the appearance of organic solutes in saliva have been in the literature for over 70 years, it has only been in the past 30 years that there has been emphasis on the appearance of drugs. Although many assumptions for drug level monitoring in saliva are made, the primary requisite for salivary monitoring to be useful is a constant or predictable relationship between the drug concentration in saliva and the drug concentration in plasma. Measurement of oral fluid drug levels for the purpose of managing patients and making dosage adjustments may be useful for select drugs or drug classes. However, it does not appear to be useful for the majority of drugs therapeutically monitored. Some work with antipsychotic medications has indicated that although the measurement of drug concentrations themselves may not be useful for dosage adjustment, the ratio of parent drug to metabolite may reflect altered metabolic status due to either pharmacogenetic variation or other clinical conditions. Furthermore, analysis of saliva may provide a cost-effective approach for the screening of large populations.

A sustained release dosage form of acyclovir for buccal application: An experimental study in dogs

Acyclovir is an antiviral agent and it has been particularly used for the treatment of herpes simplex infections. The treatment of infection in the oral cavity is often difficult, because of insufficient drug concentration in saliva when acyclovir is administered via the oral route in conventional tablet form for systemic uptake. Therefore, it was aimed to prepare a tablet for buccal administration and to investigate its effectiveness by performing in vitro and in vivo experiments.The solubility (1.559–4.584) and octanol/water partition coefficients ( − 2.176 to − 1.625) of the acyclovir were investigated at different pH conditions. A series of tablet formulations were prepared for buccal application and their dissolution properties were determined in artificial saliva medium. The effect of tablet ingredients on the release rate and mucoadhesion force was investigated. The dissolution properties of commercially available acyclovir tablets were also determined in the artificial gastric juice.Franz type diffusion cells were used to determine acyclovir penetration through buccal mucosa from prepared buccal tablets.Selected buccal tablets, commercial tablets and intravenous acyclovir solutions were administered to mongrel dogs and drug levels in the blood determined by HPLC.A pharmacokinetic model for buccal application was also developed and blood concentrations were calculated theoretically and compared with the experimental results. Prepared buccal tablets were found to be effective for the treatment of viral infections locally within the oral cavity and also for systemic treatment.

Cloud-Point Extraction for the Determination of the Free Fraction of Antiepileptic Drugs in Blood Plasma and Saliva

A method for the determination of the free fraction of antiepileptic drugs in plasma and saliva was developed. The separation of free and protein-bound fractions was obtained by cloud-point extraction under optimum conditions of pH, surfactant type, and concentration. It is shown that the free fraction of carbamazepine and of phenobarbital in plasma coincides with the drug concentration in saliva. The dependence of the free fraction in plasma on the administered dose was studied. The influence of the simultaneous administration of the two drugs on their free concentrations was revealed: In the presence of carbamazepine the free fraction of phenobarbital is decreased markedly whereas phenobarbital does not influence the behavior of carbamazepine.

Therapeutic Drug Concentration Monitoring Using Saliva Samples

In the last 30 years there has been great interest in the use of saliva in therapeutic drug monitoring. Numerous investigators have suggested that saliva be used as an alternative body fluid for the therapeutic drug monitoring of anticonvulsant drugs. Not only can saliva be obtained easily on multiple occasions with minimal discomfort to the patient but, more importantly, useful relationships exist between the saliva and blood concentrations of the most commonly used anticonvulsant drugs. The measurement of anticonvulsant drug concentrations in saliva has been applied to pharmacokinetic and pharmacodynamic studies, and for therapeutic drug monitoring in a variety of seizure disorders. However, this simple and non-invasive method is not widely accepted in clinical practice. Several recent developments in sample collection and analytical methods, and the growing interest in free drug concentrations, provide a renewed impetus for saliva sampling for therapeutic drug monitoring of anticonvulsant drugs. Salivary flow rates vary significantly both between individuals and under different conditions. The use of stimulated saliva has several advantages over resting saliva. The salivary flow rate and pH, sampling conditions, contamination and many other pathophysiological factors may influence the concentrations of the medication in saliva. However, under standardised and well-controlled sampling condition, therapeutic drug monitoring of anticonvulsant drugs in saliva can be useful for determining compliance with medication in paediatric patients, for analysing the concentration of free drug and in situations where repeated sampling is necessary. Saliva is an alternative matrix for the therapeutic drug monitoring of carbamazepine, phenytoin, primidone and ethosuximide because the concentrations of these medications in saliva reflect the concentrations of the drug in serum. This is not the case for valproic acid (valproate sodium) and some controversy exists for phenobarbital. Further studies are required to assess the clinical value of monitoring anticonvulsant drugs and their metabolites in saliva, to examine the influence of pathophysiological factors on salivary drug concentrations, to improve the design of special devices to reproducibly and conveniently collect saliva samples, and to develop and use new analytical methods to achieve more sensitive and accurate results.

Pharmacokinetics of Ofloxacin - Measurement of Drug Concentration in Saliva of Patients with Impaired Renal Function

Pharmacokinetics of Ofloxacin - Measurement of Drug Concentration in Saliva of Patients with Impaired Renal Function

Saliva testing for drugs of abuse.

Saliva testing for drugs of abuse can provide both qualitative and quantitative information on the drug status of an individual undergoing testing. Self-administration by the oral, intranasal, and smoking routes often produces "shallow depots" of drug that contaminate the oral cavity. This depot produces elevated drug concentrations that can be detected for several hours. Thereafter, saliva drug concentrations generally reflect the free fraction of drug in blood. Also, many drugs are weak bases and saliva concentrations may be highly dependent upon pH conditions. These factors lead to highly variable S/P ratios for many of the drugs of abuse. Table 3 provides a compilation of experimental and theoretical S/P (total) ratios determined for drugs of abuse. Estimations of the theoretical S/P (total) ratios for acidic and basic drugs were based on the Henderson-Hasselbalch equation. Saliva pH was assumed to be 6.8 unless reported otherwise by the investigators. Generally, there was a high correlation of saliva drug concentrations with plasma, especially when oral contamination was eliminated. Assay methodology varied considerably, indicating that saliva assays could be readily developed from existing methodology. There are many potential applications for saliva testing for drugs of abuse. Table 4 lists several general areas in which information from saliva testing would be useful. Clearly, saliva drug tests can reveal the presence of a pharmacologically active drug in an individual at the time of testing. Significant correlations have been found between saliva concentrations of drugs of abuse and behavioral and physiological effects. Results indicate that saliva testing can provide valuable information in diagnostics, treatment, and forensic investigations of individuals suspected of drug abuse. It is expected that saliva testing for drugs of abuse will develop over the next decade into a mature science with substantial new applications.

Utilization of Salivary Level Monitoring of Mexiletine in the Therapy of Arrhythmic Patients.

In order to investigate the utility of therapeutic monitoring of mexiletine aided by the saliva drug levels, serum (total and unbound fraction) and saliva drug concentrations were measured in six inpatients with ventricular arrhythmia who were given an oral daily dose of 150 or 300 mg (t. i. d.) of mexiletine hydrochloride.Mexiletine levels in saliva were consistently much higher than the levels in serum of the patients. Saliva level to total and unbound serum drug concentration ratio (S/S ratio) varied markedly among patients from 4.5 to 32.0 and from 9.6 to 68.6, respectively, on the first day of medication. The predicted levels of mexiletine in the serum on day 7 and day 14 using the mean S/S ratio obtained on the first day of medication were almost identical to the observed levels in three of these patients, who showed a small ratio of saliva to total serum concentration, less than about 9 (or 21 for the ratio to unbound concentration). There was no correlation between the mexiletine level in saliva and the salivary flow rate.Four patients who received the drug at a daily dose of 300mg showed almost favorable trough drug levels in the serum total fraction ranging from 0.164 to 0.583 μg/ml, and ventricular premature contraction (VPC) in these patients was almost completely reduced (94.7-100.0%), except for one non-responder. Two patients who received 150 mg of the drug showed steady-state trough levels in the serum total fraction of less than 0.1μg/ml and the VPC of one of these two patients was hardly controlled. We, therefore, increased the daily dose to 300 mg in this patient, who was well controlled thereafter.From these findings, it is suggested that it may be possible to estimate the serum mexiletine levels from the saliva drug levels by using the initial S/S ratios inpatients with ratios of less than about 9.

A comparison of serum and saliva paracetamol concentrations.

The relationship between serum and saliva paracetamol concentrations was investigated in twenty healthy volunteers. The plasma and saliva drug concentrations showed a significant correlation (r = 0.67). However the agreement between the two methods of measurement was poor with limits of agreement of -15.3 mg l-1 to +15.9 mg l-1 with mean sample values of 19.2 and 19.5 mg l-1 for plasma and saliva, respectively.

Antipyrine - new light on an old drug.

The time courses of analgesic activity of 4 different tablets containing different amounts of antipyrine were determined in 14 volunteers using electrical tooth pulp stimulation to elicit pain. Drug action was monitored by following somatosensory evoked potentials obtained from electroencephalographic measurements as well as pain rating and pain threshold determination. The results were compared with data obtained after administration of 1000 mg acetaminophen and two different doses of aspirin (500 and 1000 mg). At the same time drug concentration in saliva of the same volunteers was analyzed by quantitative in situ thin-layer-chromatography to investigate the pharmacokinetics. Furthermore, the in vitro drug release from the different tablets was studied with a continuous flow cell model. Antipyrine produced reliable analgesic activity. The onset of action was significantly faster than after administration of the same dose of aspirin, and the effect lasted longer than after intake of the same dose of acetaminophen. Comparison of the drug action and drug level in the body showed an excellent correlation between pharmacodynamics and pharmacokinetics. The study confirms our earlier findings on the value of somatosensory evoked potentials as a method to investigate the pharmacodynamics of weak analgesics in humans. The results also suggest to reconsider the use of antipyrine as an over-the-counter analgesic.

Serum and saliva concentrations of sulfamethoxazole and trimethoprim in adults and children: relation between saliva concentrations and in vitro activity against nasopharyngeal pathogens.

The combination sulfamethoxazole/trimethoprim (SMX/TMP) was given orally to 4 healthy adult volunteers in mean daily doses of 23.0/4.6 mg/kg body weight for 6 days. The serum and saliva concentrations of the drugs were assayed on days 1, 3 and 6. On the first day (0-12 h) there was no measurable concentration of SMX in the saliva. On days 3 and 6 the mean peak levels of SMX in saliva were 7.8 and 9.8 micrograms/ml, i.e. 8-9% of the corresponding mean peak serum levels. In contrast, the concentrations of TMP in saliva were more than twice as high as those in serum. The mean SMX/TMP ratios in saliva days 3 and 6 were 1.3 and 1.4, respectively, i.e. approximately one-twentieth of the mean SMX/TMP ratios in serum. SMX/TMP was also administered to children with serous otitis media. The drug concentrations in saliva were assayed 2-3 h after administration on days 6 and 9 of a 10-day course, with a mean daily dose of 34.5/6.9 mg/kg body weight. The mean saliva concentration of SMX in the children was slightly higher than in adults and the mean TMP concentration about half of that in adults. The mean SMX/TMP ratio in the children's saliva was 4.2. The in vitro activity of SMX/TMP 20:1 and 4:1 was determined against H. influenzae, D. pneumoniae, B. catarrhalis and group A streptococci. H. influenzae, D. pneumoniae and group A streptococci were found more susceptible to TMP than to SMX, while the reverse was true for B. catarrhalis. In the 3 former, the potentiation of SMX by TMP was more pronounced than was the potentiation of TMP by SMX, while the opposite was recorded for B. catarrhalis. The most beneficial effect of the SMX/TMP combination against nasopharyngeal pathogens was recorded for B. catarrhalis and the weakest effect for H. influenzae and group A streptococci. With the exception of B. catarrhalis, the administration of TMP alone to adults may be just as effective against nasopharyngeal pathogens as is the SMX/TMP combination in children.

Plasma and saliva theophylline levels and pulmonary function in asthmatic patients after a sustained-release theophylline preparation (‘Nuelin’ SA)

SummarySustained-release theophylline ('Nuelin SA) given twice daily in a weight-related dose to 16 asthmatic patients maintained theophylline serum levels within the therapeutic range. On Day 14, these levels were associated with a statistically significant increase in PEFR (p<0.01) from the mean pre-treatment values of 271 litres/min. The mean trough PEFR value was 20% greater and the mean PEFR at noon 41% greater than the pre-treatment value. There was a reduction in nocturnal and early morning asthma symptoms. Measurement of drug concentration in saliva is attractive since it is non-invasive. In this study, the correlation of theophylline levels in saliva and serum was good (r = 0.95). It would seem that once steady-state theophylline serum and saliva levels have been measured, monitoring of theophylline treatment using saliva measurements may be possible within the limitations reported.

The relationship between serum and saliva trimethobenzamide concentrations in man.

Six healthy volunteers provided simultaneous serum and mixed saliva specimens at various time intervals after receiving three different concentrations of trimethobenzamide HCI (total dose 800 mg) via rectal syringe on three separate occasions. Specimens were analyzed for trimethobenzamide content and the results subjected to pharmacokinetic analysis and other statistical procedures to identify characteristics of the relationship between distribution processes in these specimen types. On the basis of linear regression analysis there was a significant correlation (P less than 0.01) between saliva and serum drug content for both mean values (r = 0.94) at each sampling time and all individuals' paired data points (r = 0.72). Because of the large degree of scatter in individual pairs, the data were subjected to analysis of variance in an attempt to determine a potential source of this divergence. The relationship between serum and saliva drug concentrations was found to depend upon the time after drug administration. We conclude that a nonuniform process determines the relative degree of partitioning trimethobenzamide between serum and saliva.