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Biomedical subjects

C Marriott

Publications and source records attributed to C Marriott.

At least 37 records · Page 2Linked to original sources
PubMed2000

The influence of crystallization conditions on the morphology of lactose intended for use as a carrier for dry powder aerosols.

Lactose has been widely used as a carrier for inhalation aerosols. The carrier morphology is believed to affect the delivery of the drug. The aim of this study was to investigate the effects of crystallization conditions on the morphology of alpha-lactose monohydrate intended for use as the carrier for dry powder aerosols. The crystallization of lactose was carried out from aqueous solutions at different supersaturations, temperatures, different stages of crystallization and in the presence of different water-miscible organic solvents. The majority of lactose crystals were found to be either tomahawk-shaped or pyramidal after crystallization at an initial lactose concentration between 33-43% w/w, but these became prismatic if the lactose concentration was increased to 50% w/w. A further increase in the lactose concentration to 60% w/w led to the preparation of elongated cuboidal crystals. Higher initial lactose concentrations tended to result in the crystallization of more elongated particles. Crystallization at 40 degrees C was shown to prepare lactose crystals with a more regular shape and a smoother surface than those crystallized at 0 degrees C. Lactose particles generated during the later stage of crystallization were found to be more regular in shape with a smoother surface than those prepared in the earlier stage. The addition of 10% (v/v) methanol or ethanol or acetone to the mother liquor increased the growth rate of lactose particles whereas addition of propanol or glycerine inhibited the rate of crystal growth. Lactose crystals prepared in the presence of glycerine were more regularly shaped with a smoother surface than those prepared in the presence of ethanol or acetone. All the resultant crystals were shown to comprise alpha-lactose monohydrate. Lactose crystals could be prepared with a precisely defined morphology by means of carefully controlling the crystallization conditions.

Aerosols↗
PubMed2000

A human oral-throat cast integrated with a twin-stage impinger for evaluation of dry powder inhalers.

The aim of this study was to investigate the applicability of replacing the glass throat from a twin-stage impinger (TSI) with a human oral-throat cast. Monodisperse aerosols were used to calibrate the human oral cast-TSI at 60 L min(-1) and cut-off in particle size was compared with that of the TSI described in the British Pharmacopoeia which employs a glass throat. The amount of salbutamol sulphate (and lactose) delivered by the Cyclohaler depositing on various elements of the in-vitro model were determined. The calibration of the model containing a human oral-throat cast at 60 L min(-1) gave a particle size cut-off of 5.2 microm which was less than that of the TSI (6.3 microm). The oral-throat cast trapped more drug than the glass throat model with a formulation that employed the larger carrier (63-90 microm; P<0.05) while it trapped a lesser amount of drug with those filled with the lower size carrier (Lactochem, micronised lactose). The greater amount of lactose in the formulation that employed the larger-sized carrier (63-90 microm) was deposited closer to the inlet of the oral-throat cast than to the inlet of the glass throat model. Replacement of the glass throat in the TSI by the human oral-throat cast, leads to a change in deposition efficiency, with the cast having a higher filter efficiency and hence more aerosol particles being captured before their entry into the TSI. This should be investigated further to determine whether such a model might provide a more realistic assessment of the in-vivo characteristics of an aerosol in comparison with the TSI currently being employed, which utilises the glass throat as the portal of entry.

Administration, Inhalation↗
PubMed2000

The effects of carrier size and morphology on the dispersion of salbutamol sulphate after aerosolization at different flow rates.

We have investigated the interdependence of various factors (particle size, surface smoothness, carrier particle shape, inhalation flow rate) on the deposition of a model drug (salbutamol sulphate) after aerosolization from a model inhaler device (Rotahaler). Different batches of alpha-lactose monohydrate were prepared to have different particle size, particle shape and surface smoothness. Each batch of lactose was then mixed separately with salbutamol sulphate in a ratio of 67.5 : 1 (w/w), under similar conditions. Drug deposition from each formulation was investigated using a 4-stage liquid impinger after aerosolization at 28.3, 60.0 and 96.0 L min(-1) via a Rotahaler. At a flow rate of 28.3 L min(-1), a large portion of drug particles was not emitted from the inhaler, the % emission varying from 29.6% to 66.6% for all formulations investigated. Drug emission tended to increase with particle size of the carrier whilst fine particle fraction, fine particle dose and dispersibility appeared to increase with decreasing particle size but increasing elongation ratio of the carrier particles. Increasing the flow rate to 60.0 L min(-1) was shown to increase drug emission since > 75% total dose was found to be emitted from the inhaler. Again, smaller or more elongated lactose particles resulted in a higher fine particle dose or fine particle fraction of salbutamol sulphate than the coarser carrier, although they produced a similar (analysis of variance P > 0.05) drug emission. Increasing the flow rate to 96.0 L min(-1) did not increase drug emission. Increasing the flow rate resulted in an increase in the fine particle fraction and fine particle dose of salbutamol sulphate from all formulations. The flow rate of the airstream appeared to play the most important role, followed by particle size and elongation ratio of the carrier particles, with the surface smoothness relatively less significant in determining the deposition of salbutamol sulphate from the Rotahaler.

Aerosol Propellants↗
PubMed2000

A study of drug-carrier interactions in dry powder inhaler formulations using the Andersen cascade impactor, X-ray microanalysis and time of flight aerosol beam spectrometry (TOFABS).

The purpose of this study was to determine the in vitro deposition of both drug (albuterol sulfate) and carrier (lactose) particles in relation to each other from a dry powder inhaler formulation using an Andersen cascade impactor (ACI) and time of flight aerosol beam spectrometry (TOFABS). In addition, scanning electron microscopy (SEM) combined with X-ray microanalysis was employed to distinguish albuterol sulfate from lactose. Drug particles apparently penetrated deeper into the impactor than lactose particles contained in the formulation. In some certain stages of impactor, drug particles were separated from lactose particles. Although the TOFABS cannot distinguish between albuterol sulfate and lactose, the TOF spectra obtained from the Aerosizer would appear to be partly indicative of the interactions which exist between drug and carrier. One symmetrical TOF peak was obtained from drug or lactose alone. The TOF peak of the drug was always lower than the TOF of lactose. The times obtained for each powder between experiments were highly reproducible and typical of material and particle size. The use of SEM-X-ray microanalysis also allowed some qualitative characterization of shape and state of association of the two components.

Aerosols↗
PubMed1999

The use of different grades of lactose as a carrier for aerosolised salbutamol sulphate.

Five different grades of lactose namely, anhydrous lactose, medium lactose, regular lactose, lactose crystals and foremost lactose were fractionated under similar conditions to obtain a size range of 63-90 microm and were characterised using laser diffraction and time-of-flight particle sizing techniques, scanning electron microscopy, optical microscopy image analysis, thermal gravimetric analysis and differential scanning calorimetry. Each of these lactose fractions were then blended separately with micronised salbutamol sulphate in a ratio of 67.5:1 (w/w). The mixing uniformity and percentage recovery of salbutamol sulphate in the powder blends were analysed using a validated HPLC method. The deposition profiles of the drug were determined using a 5-stage liquid impinger after aerosolisation at 60 l min(-1) via a Rotahaler. Despite the identical processing conditions, the lactose fractions were shown to differ in particle size, size distribution and concentrations of fine particles. The particles from each fraction also exhibited different surface textures and dissimilar DSC thermograms. However, all the blends of the lactose with salbutamol sulphate were found to have a relatively high uniformity of salbutamol sulphate content, as suggested by a coefficient of variation of less than 3.2%. Anhydrous and medium lactose produced a more efficient delivery of salbutamol sulphate when aerosolised from the Rotahaler in comparison to other grades of lactose. For example, the fine particle fraction (FPF) and fine particle dose (FPD) of drug from formulations containing anhydrous lactose were 13.4+/-4.2% and 57.3+/-17.6 microg, respectively, which were approximately two times higher than the respective values of the formulation containing regular lactose. Medium lactose resulted in drug FPF (7. 9+/-2.7%) and FPD (32.4+/-11.8 microg), which were significantly (ANOVA P<0.05) higher than the same parameters obtained using lactose crystals, foremost lactose and regular lactose. More efficient drug delivery from anhydrous lactose may be partly attributed to the relatively higher concentration of fine lactose in this grade of carrier, although it showed a rougher surface than the other grades of lactose. However, the relatively high FPF of the drug from medium lactose may have been due to the relatively small mean particle size and smooth surface of the particles. Therefore, the source and grade of lactose may have a substantial effect on drug delivery from dry powder inhaler formulations and care should be taken in establishing appropriate quality control parameters when selecting an appropriate grade of carrier.

Adrenergic beta-Agonists↗
PubMed1999

Effects of particle size and adding sequence of fine lactose on the deposition of salbutamol sulphate from a dry powder formulation.

Ternary mixtures composed of coarse lactose (CL) (90.8 microm), salbutamol sulphate (SS) (5.8 microm) and either micronised lactose (ML) (5 microm) or intermediate sized lactose (IML) (15.9 microm) in a ratio of 66.5:1:1 w/w were prepared using different mixing sequences of the various components. In addition, a binary mixture composed of CL and SS (67.5:1 w/w) was also prepared as the control. The in vitro deposition of SS was measured using a twin stage impinger after aerosolisation at 60 and 90 l min-1 via a Rotahaler. The aerodynamic particle size distribution of both the aerosolised SS and lactose was further analysed using an Andersen cascade impactor at 60 l min-1. All ternary mixtures produced a significantly higher (analysis of variance, P<0.01) fine particle fraction (FPF) and fine particle dose (FPD) of SS than the control after aerosolisation at either 60 or 90 l min-1. Formulations containing the ML produced significantly (P<0.05) higher FPF and FPD of SS than those containing the IML at both aerosolisation flow rates. Different mixing sequences were also shown to result in different deposition profiles of both SS and lactose after aerosolisation of the ternary mixtures containing ML at 60 l min-1. The formulation prepared by first blending ML with CL before mixing with SS produced a higher FPF and FPD of SS but a lower FPF of lactose than the same formulation in terms of composition but prepared using different mixing orders of the three components. In contrast, the formulations containing IML produced a similar deposition profile to SS, regardless of the mixing sequences, and so did the formulations containing ML aerosolised at 90 l min-1. These results suggest that the effect of mixing sequences on drug deposition may become more prominent at lower aerosolisation flow rates and by reducing the size of any added fine lactose.

Albuterol↗
PubMed1998

Dry powder inhalers: the influence of device resistance and powder formulation on drug and lactose deposition in vitro.

It is a principal in the formulation of a dry powder aerosol that the device should enable a high fine particle fraction (FPF) of drug to be delivered to the lung whilst any carrier, such as lactose, should remain in the upper airways. Both the device and the dry powder formulation itself contribute to the resultant FPF and few studies have considered the deposition of lactose carrier. It was the purpose of this study to determine the effect of the resistance of the device and the influence of powder formulation on the deposition of drug and carrier. Measurement of the pressure drop across the devices investigated in this study showed that the two types of Inhalator Ingelheim had the highest resistance, whilst lower pressure drops were found across the Diskhaler, Cyclohaler and Accuhaler devices. The lowest pressure drops were measured across the Rotahaler and Spinhaler devices. Employing Rotacaps 400 capsules as the formulated salbutamol product, the FPF of drug was greater from the high resistance devices, being in the order Inhalators Ingelheim>Cyclohaler>Rotahaler=Spinhaler. However, the Diskhaler, employing its own developed formulation, produced the highest FPF, approximately twice that from the Accuhaler. There was no statistical difference between the FPF of salbutamol (approximately 20% nominal dose) from the Rotacaps formulation when aerosolised using high resistance devices (Inhalators Ingelheim) operated at 30 l min-1, a medium resistance device (Cyclohaler) operated at 60 l min-1 and low resistance devices (Spinhaler and Rotahaler) operated at a flow-rate of 90 l min-1. The Ventolin Diskhaler using its own formulation operated at 60 l min-1 gave a FPF of 40.33%, but the FPF obtained was sensitive to flow, being only 25.65% of the nominal dose at 30 l min-1. Whereas no lactose was found in the FPF from the Accuhaler operated at 60 l min-1, 100, 400 and 3500 microg were obtained from the Diskhaler, Rotacaps and micronised lactose formulation, respectively, when operated at the same flow-rate. An in-house formulation comprising salbutamol sulphate blended with micronised lactose in a weight ratio of 1:67.5 and aerosolised from a Cyclohaler produced a similar FPF to the Diskhaler at 60 l min-1. When air flow was reduced to 30 l min-1, the FPF from the in-house formulation was reduced considerably less than that from the Diskhaler formulation.

Adrenergic beta-Agonists↗
PubMed1997

An evaluation of two aerosol delivery systems for rhDNase.

Increasingly, proteins are delivered to the respiratory tract as an aerosol, and clinical efficacy is dependent on optimal delivery of the protein in an intact form. The object of this study was to compare the in vivo and in vitro results of two aerosol delivery systems for the aerosolization of recombinant human deoxyribonuclease I (rhDNase) in patients with cystic fibrosis (CF). Patients with CF who were to be initiated on rhDNase were randomized either to the Hudson nebulizer and Pulmo-Aide compressor or to the Sidestream nebulizer driven by the CR50 air compressor. An in vitro study was performed in six sets of the two aerosol delivery systems. One hundred and seventy three patients were randomized in this open study, where rhDNase was administered for 7 days. Improvements in pulmonary function were observed in both groups following 1 week of therapy with rhDNase. Changes in the Sidestream/CR50 and Hudson/Pulmo-Aide groups, respectively, were: 16 and 11% for forced expiratory volume in one second (p=0.14); 12 and 10% for forced vital capacity (p=0.70); and 14 and 7% for forced expiratory flow at 25-75% of expiration (FEF(25-75)) (p=0.18). A greater proportion of patients in the Sidestream/CR50 group (58%) had a >10% response in FEF(25-75) compared to the Hudson/Pulmo-Aide group (42%; p=0.03). The Sidestream nebulizer had a faster nebulization rate (p<0.05), lower mass median diameter for the aerosol mass produced (p<0.001), higher percentage of particles in the respirable range (p<0.001) and greater respirable output (p<0.005), compared to the Hudson nebulizer. The Sidestream/CR50 combination is a quicker, more efficient system in vitro than the Hudson/Pulmo-Aide combination, whereas the in vivo study only suggested a difference. Clinically, the two systems have similar efficacy.

Adult↗
PubMed1996

An in-vitro study of the effect of hydrocolloid patch occlusion on the penetration of triamcinolone acetonide through skin in man.

The aim of this study was to evaluate the effect of occlusion using hydrocolloid-containing patches on in-vitro triamcinolone acetonide (TACA) penetration of the epidermis while monitoring the uptake of water by the patches as a result of transepidermal water loss. The hydrocolloid patches were a laminate of a pressure-sensitive hydrophobic adhesive (containing a dispersion of 39% of either pectin or carmellose sodium) and a polyethylene film. The diffusion of a representative corticosteroid (TACA) through isolated epidermal sheet was shown to depend on the site from which the skin was removed. The two patch-types exhibited markedly different hydration rates when applied to the membranes. For example, after 96 h the carmellose sodium patch showed ten times the weight increase of the pectin patch. Epidermal diffusion rates were, however, similar, both showing a 3-4-fold enhancement over unoccluded conditions. The increase in TACA diffusion with the patches can be explained by the increase in skin hydration that occurs during occlusion. Despite the large differences in transepidermal water transfer through the epidermal membranes with the two types of hydrocolloid patch, however, this level of stratum corneum hydration was apparently similar. As the rate of diffusion was also independent of hydrocolloid patch component, it seems possible that the hydrophobic component of the patch matrix may also influence the level of skin hydration and consequent drug diffusion.

Adult↗
PubMed1996

In vivo effects of recombinant human DNase I on sputum in patients with cystic fibrosis.

BACKGROUND: Viscoelastic secretions in cystic fibrosis cause impaired mucus clearance and persistence of bacteria within the lung. The abnormal rheology is partly due to the presence of high molecular weight deoxyribonucleic acid (DNA). Recombinant human DNase I (rhDNase) has been shown to depolymerise DNA and thereby reduce the in vitro viscoelasticity of sputum in patients with cystic fibrosis. A phase II double blind placebo controlled study showed that rhDNase improved pulmonary function in patients with cystic fibrosis. The object of the present study was to evaluate the in vivo effects of rhDNase on sputum rheology and to determine whether these were correlated with changes in pulmonary function. METHODS: Patients were randomised to receive either placebo or rhDNase 2.5 mg twice daily for 10 days. Sputum samples were collected in sterile containers during screening and during treatment with the study drug. Pulmonary function and rheological analysis were the primary outcomes evaluated. Other parameters assessed were quantitative sputum bacteriology, sputum DNA concentration, and change in molecular mass of DNA polymers. RESULTS: The viscoelasticity of the sputum in untreated patients with cystic fibrosis was high and treatment with rhDNase reduced all the rheological parameters measured: dynamic storage modulus (a measure of elasticity), dynamic loss modulus (a measure of viscosity), and log complex modulus (a measure of mucus rigidity). The calculated cough clearance index was also improved following treatment with rhDNase. These rheological parameters showed a correlation with forced expiratory volume in one second (FEV1) which was improved by a mean (SE) of 13.3 (5.6)% on day 10 of treatment with rhDNase compared with a change of 0.2 (3.1)% in the placebo group. There was no change in bacterial colony counts or sputum DNA concentrations following treatment with rhDNase, but a small decrease in high molecular weight DNA was observed. CONCLUSIONS: Patients with cystic fibrosis treated with rhDNase show an improvement in rheological properties and pulmonary function, one of the mechanisms being a reduction in the proportion of high molecular weight DNA.

Adolescent↗
PubMed1995

The effect of hyaluronan on the in vitro deposition of diclofenac within the skin.

Hyaluronan is a glycosaminoglycan and has a protective, shock-absorbing and structure-stabilizing role in connective tissue. Recently, it has been suggested that hyaluronan can be used as a controlled and localized delivery vehicle for diclofenac in the treatment of a variety of conditions including osteoarthritic pain, basal cell carcinoma and actinic keratosis. The aim of this study was to examine the effects of hyaluronan on the in-vitro diffusion and deposition of diclofenac within the skin. The studies involved full thickness, epidermal sheet and stratum corneum human skin sections in an in-vitro Franz cell model, in which the diffusion and deposition of 14C-labelled diclofenac and 3H-labelled hyaluronan was investigated. The results showed that the diffusion of 14C-labelled diclofenac was sustained and controlled by hyaluronan as compared to a buffer control, that a depot or reservoir of the drug was formed in the epidermis and that it was probably this layer that determined the rate of release of diclofenac within the skin. 3H-labelled hyaluronan was found to penetrate all layers of the skin, although the rate of diffusion was much slower than that of labelled diclofenac. Again, most of the activity was found to be retained within the epidermis, which supports the hypothesis of the importance of this layer in the mode of action. The presence within the epidermis of potential receptors for hyaluronan has recently been confirmed, and this may partially explain the findings of the present in-vitro studies.

Administration, Cutaneous↗
PubMed1994

Tamoxifen decreases drug efflux from liposomes: relevance to its ability to reverse multidrug resistance in cancer cells?

Tamoxifen decreased the efflux of the fluorescent marker drug, chloroquine, from phosphatidylcholine liposomes. Tamoxifen is a known structural-mimic of cholesterol, which were both found to be similarly effective in preventing drug release from liposomes. This ability of tamoxifen and cholesterol to decrease drug efflux in a concentration-dependent manner is likely to arise from their known ability to decrease membrane fluidity both in liposomes and also in cancer cells. The possible importance of the ability of tamoxifen to inhibit drug efflux from liposomes in relation to its ability to reverse multidrug resistance in cancer patients caused by the efflux of cytotoxic therapeutic agents, is discussed.

Antineoplastic Agents↗
PubMed1994

Potential use of microencapsulation for sustained drug delivery to the respiratory tract.

Microencapsulation has long been regarded as a means of achieving sustained drug delivery. In these studies, a spray drying technique was used to produce salbutamol-loaded albumin microparticles with a view to formulating a controlled release system to be used in respiratory drug delivery. Encapsulation efficiencies (40-60 % w/w) obtained using this technique compared very favourably with those obtained using emulsification procedures (1-2 % w/w).

Albuterol↗
PubMed1993

Bromhexine plus oxytetracycline: the effect of combined administration upon the rheological properties of mucus from the mini-pig.

Three adult mini-pigs were employed to assess the effects of a twice daily dosage (40 mg kg-1) of oxytetracycline hydrochloride (OTC) and a combination of OTC with (0.5 mg kg-1) bromhexine hydrochloride (BHC) on the rheological properties and wet weight of secreted tracheal mucus. Mucus was collected daily from open-ended tracheal pouches established surgically in the mini-pigs. After a five day control period, either OTC or OTC plus BHC was administered twice daily with the normal diet. Each study period was followed by a five day washout period when mucus was collected but no drug given. The viscoelastic properties of each mucus sample were determined using creep compliance analysis. OTC was shown to increase the residual shear viscosity IP < 0.01) and increase the instantaneous compliance (P < 0.01). An increase in the wet weight of the collected mucus occurred in one pig only (P < 0.01). When BHC was co-administered with OTC, all of these changes were abolished. Evidence was obtained to suggest that BHC increased the concentration of OTC within the secreted mucus. BHC appeared to reverse the mucospissic activity of OTC in-vivo.

Animals↗
PubMed1993

No added benefit from nebulized amiloride in patients with cystic fibrosis.

In cystic fibrosis (CF) airway epithelial sodium absorption is increased 2-3 fold. Since sodium absorption is inhibited by the sodium channel blocker amiloride, our aim was to assess its therapeutic benefit in cystic fibrosis. A randomized, double-blind, placebo-controlled, cross-over trial of nebulized amiloride was performed in 23 patients with cystic fibrosis. Amiloride or placebo was administered four times daily for two six month periods. Existing treatment was continued, and any infective exacerbations treated in the usual way. Fourteen patients completed the study. No significant changes occurred in forced expiratory volume in one second, forced vital capacity, oxygen saturation, body weight, sputum volume, culture and rheology, serum urea, and electrolytes, white cell count and erythrocyte sedimentation rate during either treatment period. The frequency of infective exacerbations was also not different in either treatment period. We were thus unable to confirm the benefit shown in the only other clinical trial of nebulized amiloride in cystic fibrosis and conclude that, in the presence of established treatment for cystic fibrosis lung disease, nebulized amiloride offers no additional clinical benefit.

Administration, Intranasal↗
PubMed1992

Blockade of insulin sensitive steady-state R-type Ca2+ channel by PN 200-110 in heart and vascular smooth muscle.

The effect of high K+ concentration, insulin and the L-type Ca2+ channel blocker PN 200-110 on cytosolic intracellular free calcium ([Ca2+]i) was studied in single ventricular myocytes of 10-day-old embryonic chick heart, 20-week-old human fetus and rabbit aorta (VSM) single cells using the Ca(2+)-sensitive fluorescent dye, Fura-2 microfluorometry and digital imaging technique. Depolarization of the cell membrane of both heart and VSM cells with continuous superfusion of 30 mM [K+]o induced a rapid transient increase of [Ca2+]i that was followed by a sustained component. The early transient increase of [Ca2+]i by high [K+]o was blocked by the L-type calcium channel antagonist nifedipine. However, the sustained component was found to be insensitive to this drug. PN 200-110 another L-type Ca2+ blocker was found to decrease both the early transient and the sustained increase of [Ca2+]i induced by depolarization of the cell membrane with high [K+]o. Insulin at a concentration of 40 to 80 microU/ml only produced a sustained increase of [Ca2+]i that was blocked by PN 200-110 or by lowering the extracellular Ca2+ concentration with EGTA. The sustained increase of [Ca2+]i induced by high [K+]o or insulin was insensitive to metabolic inhibitors such as KCN and ouabain as well to the fast Na+ channel blocker, tetrodotoxin and to the increase of intracellular concentrations of cyclic nucleotides. Using the patch clamp technique, insulin did not affect the L-type Ca2+ current and the delayed outward K+ current. These results suggest that the early increase of [Ca2+]i during depolarization of the cell membrane of heart and VSM cells with high [K+]o is due to the opening and decay of an L-type Ca2+ channel. However, the sustained increase of [Ca2+]i during a sustained depolarization is due to the activation of a resting (R) Ca2+ channel that is insensitive to lowering [ATP]i and sensitive to insulin.

Animals↗
PubMed1992

Bile salt- and lysophosphatidylcholine-induced membrane damage in human erythrocytes.

The interaction of bile salts and lysophosphatidylcholine (LPC) with membranes has implications both in understanding the aetiology of a number of gastrointestinal disorders, including gastritis, gastric ulcers and colonic cancer, and in enhancing drug absorption by various epithelia. The membrane toxicity of nine bile salts (the sodium (S) salts of chenodeoxycholate (CDC), deoxycholate (DC) and cholate (C) and their glycine (G) and taurine (T) conjugates) and LPC was determined using erythrocyte haemolysis as a model parameter. Washed human erythrocytes were incubated for 15-60 min at 20 degrees C with media buffered at pH 8, 7 and 6. Bile salt toxicity was shown to be a function of type, concentration, pH and contact time with the membrane. At pH 7 toxicity decreased in the order LPC greater than unconjugated dihydroxy salts (SDC and SCDC) greater than conjugated deoxycholates (SGDC and STDC) greater than conjugated chenodeoxycholates (SGCDC and STCDC) greater than unconjugated trihydroxy salt (SC) greater than conjugated trihydroxy salts (SGC and STC). Incubation with equimolar combinations of bile salts (SDC+SCDC; STCDC+SGDC; SDC+STDC) indicated that the resultant damage was an additive function of the damage induced by the individual bile salts.

Bile Acids and Salts↗