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PubMed2003

The effect of ketoconazole on the in vivo intestinal permeability of fexofenadine using a regional perfusion technique.

AIMS: To investigate whether the drug-drug interaction between fexofenadine and ketoconazole is localized to efflux transport proteins of the small intestine, and to determine and classify the effective jejunal permeability (Peff) of fexofenadine according to the Biopharmaceutics Classification System (BCS). METHODS: Two separate jejunal perfusion experiments were performed using the Loc-I-Gut technique in eight healthy volunteers. During treatment 1 (T1), we investigated the acute effect of ketoconazole on the Peff and plasma pharmacokinetics of fexofenadine. In treatment 2 (T2) we examined the effect of oral pretreatment with ketoconazole (200 mg daily for 5 days) on the same absorption parameters. Each experiment was divided into two periods of 100 min and the jejunal segment was perfused with 93 micro m fexofenadine during both periods. In period 2 of each treatment, fexofenadine was coadministered with 94 micro m ketoconazole. The concentrations of fexofenadine in intestinal perfusate and plasma were measured by liquid chromatography with mass detection. RESULTS: During T1, the mean (+/- s.d.) Peff of fexofenadine was low according to the BCS (0.11 +/- 0.11 and 0.04 +/- 0.13 x 10(-4) cm s(-1) in periods 1 and 2, respectively), and the coadministration of ketoconazole in period 2 had no significant acute effect on Peff (95% confidence interval (CI) on the difference -0.37, 0.51). After pretreatment with ketoconazole (T2), the jejunal Peff of fexofenadine increased to 0.29 +/- 0.47 and 0.22 +/- 0.31 x 10-4 cm s(-1) in both periods 1 and 2, respectively, but the change was not statistically significant when compared with T1 (95% CI on the difference -0.62, 0.27 for T1 0-100 min vs T2 0-100 min; -0.54, 0.34 for T1 0-100 min vs T2 100-200 min). Fexofenadine plasma AUC from 0-100 mg showed no significant difference after pretreatment with ketoconazole (55 +/- 101 and 51 +/- 33 micro g ml(-1) min(-1) respectively; 95% CI on the difference -108, 115). Total plasma AUC (0-720 min) was 318 +/- 426 and 426 +/- 232 ng ml(-1) min in T1 and T2, respectively (95% CI on the difference -622, 405). CONCLUSIONS: No significant effect of acute coadministration or pretreatment with ketoconazole on the in vivo intestinal absorption of fexofenadine was detected in this study.

Adult↗

PubMed2000

2-hydroxypropyl-beta-cyclodextrin increases aqueous solubility and photostability of all-trans-retinoic acid.

BACKGROUND: All-trans-retinoic acid (ATRA, vitamin A acid or tretinoin) is effective in the treatment of acute promyelocytic leukaemia (APL). Unfortunately, the oral absorption of ATRA is highly variable. Its poor aqueous solubility also makes it difficult to be formulated into parenteral formulation. To date, there is no parenteral formulation of ATRA available commercially. OBJECTIVE: To undertake the preformulation work necessary for developing such a product. METHOD: We investigated the solubility and stability profile of ATRA in various formulations. RESULTS: The aqueous solubility of ATRA could be greatly increased by the inclusion of ATRA in 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD). Adjusting the pH value further improved the water solubility of ATRA. The photostability of HP-beta-CD-based formulation of ATRA was evaluated and it was found that inclusion ATRA into HP-beta-CD did improve the photostability of ATRA. CONCLUSION: These results showed that it is possible to develop a parenteral formulation and/or an aqueous oral formulation of all-trans-retinoic acid by using 2-hydroxypropyl-beta-cyclodextrin. However, the biopharmaceutical properties of such a formulation would be necessary before its use.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMedDate not supplied

The Academy of Managed Care Pharmacy Format for Formulary Submissions: an evolving standard--a Foundation for Managed Care Pharmacy Task Force report.

OBJECTIVE: The objective of this report is to provide, in detail, the evidentiary requirements contained in Version 2.0 of the Academy of Managed Care Pharmacy's (AMCP's) Format for Formulary Submissions and to elaborate on several key issues regarding the use of the Format that users, potential users, and pharmaceutical manufacturers have raised since AMCP published the first version of the guidelines in October 2000. BACKGROUND: The AMCP published its Format for Formulary Submissions in October 2000. The AMCP leadership and its members were motivated to develop these guidelines by a growing need to ensure that any increased utilization of medications, biopharmaceuticals, and vaccine products was appropriate and that newer products would bring added clinical and economic value to covered populations. Since publication of the Format, it has garnered nationwide publicity and attracted considerable positive and negative attention. As adoption of the AMCP Format has spread, manufacturers have begun to standardize the framework within which they present population-specific data. Since publication of the AMCP Format, the AMCP and the Foundation for Managed Care Pharmacy (FMCP) have continuously sought input from pharmaceutical manufacturers and health-system pharmacists through various venues to improve and clarify the process. Version 2.0 is the first attempt to address user's comments and concerns. METHODS: The majority of the article text is taken directly from Version 2.0 of the AMCP Format for Formulary Submissions published by the AMCP in October 2002. CONCLUSION: The AMCP and the FMCP believe that the AMCP Format is a tool that will help health systems establish a record of commitment to rational decision making, thus gaining the confidence of patients, clinicians, and members. While providing manufacturers a vehicle for communicating the scientifically based value of their product to a health system, the required evidence to substantiate that value argument allows a pharmacy and therapeutics committee to determine the clinical benefits of a drug, verify any cost savings the drug may generate, and determine the overall cost consequences to their health system. The AMCP Format for Formulary Submissions is an essential tool to evaluate medications, but requires thoughtful consideration as it is used.

Academies and Institutes↗

PubMed2002

Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.

BACKGROUND: Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrP(vCJD)), human sporadic CJD (PrP(sCJD)) and Gerstmann-Sträussler-Scheinker (PrP(GSS)) syndrome was compared to the partitioning of hamster scrapie (PrP(Sc)) in three plasma protein purification steps. Sheep scrapie (PrP(Sc)) was similarly evaluated. STUDY DESIGN AND METHODS: The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrP(vCJD), human PrP(sCJD), human PrP(GSS), sheep PrP(Sc), and hamster 263K PrP(Sc). The partitioning of the pathogenic form of the PrP was analyzed. RESULTS: Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrP(Sc). A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (> or = 3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. CONCLUSIONS: These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.

Animals↗

PubMed1998

Research and development commitments in an integrated plasma collection and plasma fractionation environment.

Plasma fractionation has emerged as one of the most scientifically demanding fields in the biopharmaceutical area. Producing safe plasma derivatives implies the development, use, and proper understanding of sensitive testing technologies to detect infection markers in starting plasma. It also requires the implementation of carefully selected, nondenaturing, efficient plasma protein purification and viral reduction technologies that do not alter the physiological functions and clinical potential of plasma proteins. Success in this field can be achieved only by a strong commitment to sustain constant research and development of projects targeting the production of safer and innovative plasma products.

Blood Coagulation Factors↗

PubMed2000

St John's Wort: effect on CYP3A4 activity.

BACKGROUND: St John's Wort is a widely used herbal product. Information regarding its potential for drug interactions is required for responsible treatment of patients using St John's Wort. CYP3A4 is a metabolic enzyme implicated in most clinically significant drug-drug interactions. OBJECTIVE: To determine the in vivo effect of reagent-grade St John's Wort extract on CYP3A4 activity through evaluation of urinary 6-beta-hydroxycortisol/cortisol ratios. METHODS: Thirteen subjects ranging in age from 18 to 25 years participated in this unblinded, multiple-dose, single-treatment before-after trial conducted in a university-based pharmacokinetics and biopharmaceutics laboratory. Each subject ingested a 300-mg tablet of reagent-grade St John's Wort extract standardized to 0.3% hypericin three times a day for 14 days. Baseline and posttreatment CYP3A4 activity was assessed with the urinary 6-beta-hydroxycortisol/cortisol ratio after a 24-hour urine collection. RESULTS: The mean +/- SD urinary 6-beta-hydroxycortisol/cortisol ratio significantly increased (P = .003) from a baseline value of 7.1 +/- 4.5 to 13 +/- 4.9. The mean +/- SD percentage increase was 114% +/- 95%, with a range from -25% to 259%. All but one subject had an increase in the ratio. CONCLUSIONS: Treatment with St John's Wort for 14 days resulted in significant increases in the urinary 6-beta-hydroxycortisol/cortisol ratio. This finding suggests that St John's Wort is an inducer of CYP3A4.

Adolescent↗

PubMed2001

Nuclear transfer in human medicine and animal breeding.

Cloning has a number of potential applications in human medicine and animal breeding, but the efficiency of production of developmentally competent embryos and healthy animal offspring needs to be improved. The primary deficiency appears to be incomplete or abnormal nuclear reprogramming after nuclear transfer, and it is hypothesized that epigenetic regulators of transcription cannot always be converted to the embryonic pattern and this leads to implantation failure, gestational abnormalities and poor health of offspring. Research needs to be focused on this aspect of development for nuclear transfer embryos. However, there is a gradual demand for commercial application for cloning in animal production, transgenesis and animal biopharmaceuticals, particularly in milk. These applications will expand in the near future. There is little application of nuclear transfer in human medicine at present, but important applications may be demonstrated for prevention of the inheritance of mitochondrial mutations, prevention of age-related aneuploidis in women, artificial gametes for sterile individuals or couples and for therapeutic cloning to enable cell and gene therapies.

Animal Husbandry↗

PubMed2002

Antiviral and antitumor peptides from insects.

Insects can rapidly clear microbial infections by producing a variety of immune-induced molecules including antibacterial and/or antifungal peptides/polypeptides. In this report, we present the isolation, structural characterization, and biological properties of two variants of a group of bioactive, slightly cationic peptides, referred to as alloferons. Two peptides were isolated from the blood of an experimentally infected insect, the blow fly Calliphora vicina (Diptera), with the following amino acid sequences: HGVSGHGQHGVHG (alloferon 1) and GVSGHGQHGVHG (alloferon 2). Although these peptides have no clear homologies with known immune response modifiers, protein database searches established some structural similarities with proteins containing amino acid stretches similar to alloferon. In vitro experiments reveal that the synthetic version of alloferon has stimulatory activities on natural killer lymphocytes, whereas in vivo trials indicate induction of IFN production in mice after treatments with synthetic alloferon. Additional in vivo experiments in mice indicate that alloferon has antiviral and antitumoral capabilities. Taken together, these results suggest that this peptide, which has immunomodulatory properties, may have therapeutic capacities. The fact that insects may produce cytokine-like materials modulating basic mechanisms for human immunity suggests a source of anti-infection and antitumoral biopharmaceuticals.

Amino Acid Sequence↗

PubMedDate not supplied

Immune modulator studies in primates: the utility of flow cytometry and immunohistochemistry in the identification and characterization of immunotoxicity.

Exposure to natural environmental products, biopharmaceuticals, or investigational adjuvants has the potential to negatively impact the immune system, resulting in either up- or downregulation of immune function (immunomodulation). Many current protocols for primate toxicologic testing call for the evaluation of changes in immune cell number (peripheral blood or tissue), alterations in the weights of immune system organs (lymph nodes, spleen, thymus), and/or increases in the overall incidence of infections or neoplasms; these data are relied upon to suggest altered immune function. However, these are informative only when clear differences in frequency and/or severity of effects can be distinguished across control and dosed groups. In the absence of such distinct morphologic or clinical pathologic changes, the identification of potential immunomodulatory effects can present a much greater challenge. Additional evaluations may be needed to detect altered immune system integrity; these are based on in vivo assessments in primates of cellular or humoral responsiveness. Immunomodulatory effects can be characterized by in vitro or in vivo immune function tests: these tests require prestudy planning to integrate assessments into ongoing toxicology programs. These methods also involve specialized training and equipment, particularly if the intent is to evaluate parameters in a GLP laboratory setting. In primate toxicology, the added costs required to perform a complete functional analysis of the immune system can be substantial, but may be warranted depending on the clinical development plans. Two analytical methods that are easily incorporated into the standard toxicology profile in primates are flow cytometry and immunohistochemistry. Flow cytometry (FC) is used to assess changes in the relative distribution of immune cell marker expression, and where marker expression is known to fluctuate with the state of cell activation, can also provide information on functional attributes of immune cells. Immunohistochemistry (IHC) provides a means to evaluate similar characteristics of immune cells within tissue sections. Used together, FC and IHC can aid in the identification of changes in immune system that may not be apparent by traditional testing procedures (such as H&E staining), thus aiding in the characterization of immune system alterations. This presentation focused on the utility of flow cytometry and immunohistochemistry in a standard primate toxicology evaluation, with representative examples showing the benefits of these technologies in the diagnosis of potential immunomodulatory effects.

Adjuvants, Immunologic↗

PubMed1997

An immunoligand assay for quantitation of process specific Escherichia coli host cell contaminant proteins in a recombinant bovine somatotropin.

We have developed a Threshold System immunoligand assay for the quantitation of residual, process-specific, Escherichia coli host cell contaminant proteins (HCP) in somavubove (a normal sequence recombinant bovine somatotropin). The assay has a dynamic range of 2 to 160 ng/mL, with a limit of quantitation of 2 ng/mL. Daily analytical precision (CV) for six replicates of the designated somavubove laboratory standard is 3.0%. Cumulative analytical precision for multiple assay runs of this standard (a total of 69 laboratory standard replicates) is 8.4%. A conservative alert limit of 100 ng/mL has been assigned in order to assure analytical precision for each assay sample under conditions of stoichiometric antibody excess. Although the assay was designed for use as a profile-release specification assay, it has also been used to validate removal of HCP by the proprietary somavubove purification process. This use is consistent with regulatory guidelines related to "well characterized" recombinant biopharmaceutical proteins.

Animals↗

PubMedDate not supplied

The influence of magnesium stearate on the characteristics of mucoadhesive microspheres.

Microspheres containing the mucoadhesive polymer chitosan hydrochloride, with matrix polymer Eudragit RS, pipemidic acid as a model drug and agglomeration preventing agent magnesium stearate were prepared by the solvent evaporation method. The amount of magnesium stearate was varied and the following methods were used for microsphere evaluation: sieve analysis, drug content and dissolution determination, scanning electron microscopy, x-ray diffractometry, DSC and FTIR spectroscopy. The results showed that average particle size decreased with increasing amount of magnesium stearate used for microsphere preparation. This is probably a consequence of stabilization of the emulsion droplets with magnesium stearate. Higher pipemidic acid content in the microspheres was observed in larger particle size fractions and when higher amounts of magnesium stearate were used. It was also found that these two parameters significantly influenced the dissolution rate. The important reason for the differences in drug content in microspheres of different particle sizes is the diffusion of pipemidic acid from the acetone droplets in liquid paraffin during the preparation procedure. The physical state of pipemidic acid changed from crystalline to mostly amorphous with its incorporation in microspheres, as shown by x-ray diffractometry and differential scanning calorimetry. No differences were observed in the physical state of pipemidic acid and in microsphere shape and surface between different size fractions of microspheres, prepared with different amounts of magnesium stearate. Additionally, no correlation between the physical state of the drug in different microspheres and their biopharmaceutical properties was found.

Acrylic Resins↗

PubMed2006

Supersaturation produces high bioavailability of amorphous danazol particles formed by evaporative precipitation into aqueous solution and spray freezing into liquid technologies.

The bioavailability of high surface area danazol formulations was evaluated in a mouse model to determine what effect high supersaturation, as measured in vitro, has on the absorption of a poorly water soluble drug. Danazol, a biopharmaceutics classification system II (BCS II) compound, was used as the model drug. Evaporative precipitation into aqueous solution (EPAS) and spray freezing into liquid (SFL) technologies were used to prepare powders of danazol/PVP K-15 in a 1:1 ratio. The evaporative precipitation into aqueous solution (EPAS) and SFL compositions, physical mixture and commercial product were dosed by oral gavage to 28 male Swiss/ICR mice for each arm of the study. Samples were taken at time points ranging from 0.5 to 24 h. Pooled mouse serum was analyzed for danazol by high performance liquid chromatography (HPLC). Powders were analyzed for their ability to form supersaturated solutions through dissolution at concentrations of 1 mg/mL which was the dose delivered to the mouse models. Spray freezing into liquid (SFL) and EPAS compositions displayed higher C(max) at 392.5 ng/mL and 430.1 ng/mL, respectively, compared to the physical mixture (204.4 ng/mL) and commercially available danazol (199.3 ng/mL). The T(max) for all compositions studied was near the 1 h time point. The area under the curve (AUC) for the SFL composition was 2558 ng.h/mL compared to EPAS composition at 1534 ng.h/mL. The area under the curve (AUC) for the physical mixture and commercially available danazol were 672 ng.h/mL and 1519 ng.h/mL, respectively. The elimination rate constants for the EPAS composition, SFL composition, and physical mixture were similar at approximately 0.15 h(-1) where as the commercially available danazol capsules displayed an elimination rate constant of 0.103 h(-1). The extent of danazol absorption in the mouse model was higher for SFL composition compared to the less amorphous EPAS composition, physical mixture, and commercially available danazol powders. Both EPAS and SFL compositions were able to form supersaturated solutions. However, the SFL composition displayed a supersaturation of 33% above control and was able to maintain supersaturation for 90 min compared to the EPAS composition (27% supersaturation above control for 60 min). Through the use of a testing method for supersaturation, it was found that EPAS and SFL compositions achieve higher apparent solubilities when compared to the physical mixture and commercially available danazol capsules. Because of the greater extent of dissolution of the SFL composition, the bioavailability was enhanced in a mouse model.

Algorithms↗

PubMed1998

Statistical methodology for screening studies with qualitative/quantitative mixtures.

A statistical method for designing screening studies involving several experimental treatments compared to a standard treatment is developed. The screening study identifies the most promising experimental treatments, which then undergo more rigorous evaluation in a future, larger study. The technique is especially relevant for biopharmaceutical research and development in which phase II clinical trials are conducted to identify the most promising drug regimens, which then move on to phase III of clinical development. It is assumed that the underlying distribution of the primary efficacy random variable is a qualitative/quantitative mixture. The proposed methodology involves calculating the probability of accepting each experimental treatment compared to the standard treatment, where the criterion for acceptance is based on the proportion of qualitative observations and a measure of their location. The probability of acceptance is displayed in two dimensions using operating characteristic contour plots. The techniques are illustrated with some practical examples and some extensions are indicated.

Algorithms↗

PubMed1998

Hypothesis testing and confidence interval construction in 2 x 2 tables of correlated proportions.

The 2 x 2 table is an invaluable tool for displaying bivariate binary data. It is easy to find examples of correlated binary response in biopharmaceutical experiments and clinical research and analysis of these data is a current research topic. The most common hypothesis tested for 2 x 2 tables of correlated proportions is that of homogeneity of the marginal proportions or, equivalently, the hypothesis of table symmetry. The 2 x 2 table of correlated proportions is rich with information and we present a survey of some of the analyses relevant for these data. Using asymptotic theory, we develop estimators of relevant parameters and associated test statistics that are of interest. We discuss interval estimation using arguments proposed by Quesenberry and Hurst (1) and Goodman (2). These interval estimators do not rely on estimation of the covariance matrix and are not necessarily equivalent to those obtained using modified chi-square statistics.

Analysis of Variance↗

PubMed2006

Supressive effect of maslinic acid from pomace olive oil on oxidative stress and cytokine production in stimulated murine macrophages.

The pentacyclic triterpene maslinic acid (MA) is a natural compound present in the non glyceride fraction of pomace olive oil, also called orujo olive oil. This compound has previously demonstrated antioxidant properties against lipid peroxidation in vitro, but its effects on reactive oxygen and nitrogen-derived species and pro-inflammatory cytokines generated by a cell system have not yet been investigated. In this study, we have tested the effect of MA upon oxidative stress and cytokine production using peritoneal murine macrophages. MA significantly inhibited the enhanced production of nitric oxide (NO) induced by lypopolysaccharide (LPS) when it was measured by the nitrite production with an inhibitory concentration 50% value (IC(50)) of 25.4 microM. This inhibiting effect seems to be consequence of an action at the level of the LPS-induction of the inducible nitric oxide synthethase (iNOS) gene enzyme expression rather than to a direct inhibitory action on enzyme activity. The secretion of the inflammatory cytokines interleukine-6 and TNF-a from LPS-stimulated murine macrophages was also significantly reduced (p < 0.05 and 0.01) by 50 and 100 microM of MA. In addition, reactive oxygen species were measured after stimulation with phorbol-12-myristate-13-acetate (PMA). Thus, pre-treatment with MA reduced the generation of hydrogen peroxide from stimulated macrophages in a dose-dependent manner (IC(50): 43.6 microM) as assayed by the oxidation of the peroxidase enzyme. However, no inhibitory effect on superoxide release, measured by the reduction of ferricytochrome c, was observed after the pretreatment with MA in the culture medium. These results suggest a potential biopharmaceutical use of this hydroxy-pentacyclic triterpene derivative, present in orujo olive oil, on preventing oxidative stress and pro-inflammatory cytokine generation.

Animals↗

PubMedDate not supplied

Microencapsulation of superoxide dismutase into biodegradable microparticles by spray-drying.

The aim of this work was to encapsulate superoxide dismutase (SOD) into biodegradable microparticles by spray-drying technique. The nature of the organic solvent to dissolve the polymer, the method of incorporation of the drug in the organic phase (with or without a surfactant, namely sucrose ester of HLB = 6), the surfactant/polymer ratio, and the nature of the biodegradable polyesters were investigated as formulation variables. The polyesters investigated as matrix were poly(epsilon-caprolactone) (PCL), poly(d, l, lactide-co-glycolide) (PLG-RG756), and poly(d, l-lactide) (PLA-R207) of respective molecular weight 78.2 kDa, 84.8 kDa, and 199.8 kDa. At surfactant/polymer ratio of 1/10, the SOD-retained enzymatic activities were higher (> 95%) for PLG-RG756 and PLA-R207 but relatively lower for the PCL (approximately 85%) probably due to the PCL relatively higher hydrophobicity. The obtained microparticles exhibited average volume mean diameter of 4-10 microm, the smaller for PCL and the larger for PLG-RG756 polymeric matrix. The in vitro release profile showed that SOD was completely (100%) released from PLA-R207 in 48 hr and from PLG-RG756 and PCL within 72 hr. These results showed that spray-drying with incorporation of surfactant such as sucrose ester may efficiently encapsulate SOD into biodegradable microparticles. Such formulations may improve the bioavailability of SOD and similar biopharmaceuticals.

Algorithms↗

PubMed1999

The distribution of the maximum likelihood estimator in up-and-down experiments for quantal dose-response data.

Standard maximum likelihood logistic or probit regression has been used in biopharmaceutical practice for inference about tolerance threshold distributions in situations where subjects (patients) have been allocated doses according to an up-and-down design. For example, a steeper dose-response curve than expected was reported in one such study. This article demonstrates that the maximum likelihood estimator systematically and considerably exaggerates the regression parameter with moderately large sample sizes. Thus a probable explanation for finding a steeper curve than expected is the method used to analyze the experiment, that is, the bias in the maximum likelihood estimator. An additional consequence of this bias is that the mean/median/ED50 are estimated with a misleading precision. In particular, confidence intervals are much too narrow. As a conclusion, we warn against conventional logistic or probit regression in combination with up-and-down designs.

Animals↗

PubMed2003

Bayesian analysis of a multivariate null intercept errors-in-variables regression model.

Longitudinal data are of great interest in analysis of clinical trials. In many practical situations the covariate can not be measured precisely and a natural alternative model is the errors-in-variables regression models. In this paper we study a null intercept errors-in-variables regression model with a structure of dependency between the response variables within the same group. We apply the model to real data presented in Hadgu and Koch (Hadgu, A., Koch, G. (1999). Application of generalized estimating equations to a dental randomized clinical trial. J. Biopharmaceutical Statistics 9(1):161-178). In that study volunteers with preexisting dental plaque were randomized to two experimental mouth rinses (A and B) or a control mouth rinse with double blinding. The dental plaque index was measured for each subject in the beginning of the study and at two follow-up times, which leads to the presence of an interclass correlation. We propose the use of a Bayesian approach to model a multivariate null intercept errors-in-variables regression model to the longitudinal data. The proposed Bayesian approach accommodates the correlated measurements and incorporates the restriction that the slopes must lie in the (0, 1) interval. A Gibbs sampler is used to perform the computations.

Bayes Theorem↗