Calibration of an in-situ fluorescence-based sensor platform for reliable BOD5 measurement in wastewater.

Reliance on biochemical oxygen demand (BOD5) as an indicator of wastewater quality has hindered the development of efficient process control due to the associated uncertainty and lag-times. Surrogate measurements have been proposed, with fluorescence spectroscopy a promising technique. Yet, assessment of in-situ fluorescence sensors across multiple wastewater treatment plants (WwTPs), and at different treatment stages, is limited. In this study a multi-parameter sonde (two fluorescence peaks, turbidity, temperature and electrical conductivity) was used to provide a BOD5 surrogate measurement. The sonde was deployed at three WwTPs, on post primary settlement tanks (PST) and final effluent (FE). Triplicate laboratory measurements of BOD5, from independent laboratories were used to calibrate the sensor, with high variability apparent for FE samples. Site and process specific sensor calibrations yielded the best results (R2cv = 0.76-0.86; 10-fold cross-validation) and mean BOD5 of the three laboratory measurements improved FE calibration. When combining PST sites a reasonable calibration was still achieved (R2cv = 0.67) suggesting transfer of sensors between WwTPs may be possible. This study highlights the potential to use online optical sensors as robust BOD5 surrogates in WwTPs. However, careful calibration (i.e. replicated BOD5 measurements) is required for FE as laboratory measurements can be associated with high uncertainty.

High frequency fluorescence monitoring reveals new insights into organic matter dynamics of an urban river, Birmingham, UK.

Natural organic matter (NOM) is fundamental to many biogeochemical processes in river ecosystems. Currently, however, we have limited knowledge of NOM dynamics across the spectrum of flow conditions as previous studies have focused largely on storm events. Field deployable fluorescence technology offers new opportunities to explore both stochastic and predictable diel NOM dynamics at finer time-steps and for longer periods than was hitherto possible, thus yielding new insight into NOM sources, processing, and pathways. Hourly fluorescence data (humic-like fluorescence [Peak C] and tryptophan-like fluorescence [Peak T]) and a suite of hydro-climatological variables were collected from an urban river (Birmingham, UK). We explored monthly concentration-discharge (C-Q) patterns using segmented regression and assessed hysteretic and flushing behaviour for Peak C, T and turbidity to infer source zone activation. Diel patterns were assessed during low flow periods. Wavelet analysis identified strong diurnal variations in Peak C with early morning peaks while no diel dynamics were apparent for Peak T. Using generalised linear modelling relationships between Peak C periodicity and both solar radiation and time since previous storm/scouring event were identified. Breakpoints and positive slopes for C-Q relationship highlighted chemodynamic behaviour for NOM over most of the monitoring period, with Peak T mobilised more relative to Peak C during high Q. Hysteresis patterns were highly variable but flushing behaviour of Peak T and C suggested exhaustion of humic compounds during long duration events and following successive rainfall events. Peak T flushing was correlated with Q magnitude highlighting the potential for combined sewer overflows to act as important NOM sources despite significant dilution potential. This research highlights the potential of real-time, field deployable fluorescence spectroscopy as a viable method for providing insight into diel and transport driven NOM dynamics.

In situ tryptophan-like fluorometers: assessing turbidity and temperature effects for freshwater applications.

Tryptophan-like fluorescence (TLF) is an indicator of human influence on water quality as TLF peaks are associated with the input of labile organic carbon (e.g. sewage or farm waste) and its microbial breakdown. Hence, real-time measurement of TLF could be particularly useful for monitoring water quality at a higher temporal resolution than available hitherto. However, current understanding of TLF quenching/interference is limited for field deployable sensors. We present results from a rigorous test of two commercially available submersible tryptophan fluorometers (ex ∼ 285, em ∼ 350). Temperature quenching and turbidity interference were quantified in the laboratory and compensation algorithms developed. Field trials were then undertaken involving: (i) an extended deployment (28 days) in a small urban stream; and, (ii) depth profiling of an urban multi-level borehole. TLF was inversely related to water temperature (regression slope range: -1.57 to -2.50). Sediment particle size was identified as an important control on the turbidity specific TLF response, with signal amplification apparent <150 NTU for clay particles and <650 NTU for silt particles. Signal attenuation was only observed >200 NTU for clay particles. Compensation algorithms significantly improved agreement between in situ and laboratory readings for baseflow and storm conditions in the stream. For the groundwater trial, there was an excellent agreement between laboratory and raw in situ TLF; temperature compensation provided only a marginal improvement, and turbidity corrections were unnecessary. These findings highlight the potential utility of real time TLF monitoring for a range of environmental applications (e.g. tracing polluting sources and monitoring groundwater contamination). However, in situations where high/variable suspended sediment loads or rapid changes in temperature are anticipated concurrent monitoring of turbidity and temperature is required and site specific calibration is recommended for long term, surface water monitoring.

The use of invertebrates as indicators of environmental change in alpine rivers and lakes.

In alpine regions climatic change will alter the balance between water sources (rainfall, ice-melt, snowmelt, and groundwater) for aquatic systems, particularly modifying the relative contributions of meltwater, groundwater and rain to both rivers and lakes. While these changes are expected to have implications for alpine aquatic ecosystems, little is known about potential ecological tipping points and associated indicator taxa. We examined changes in biotic communities along a gradient of glacier influence for two study systems: (1) a stream network in the French Pyrénées; and (2) a network of lakes in the Italian Alps, with the aim of identifying potential indicator taxa (macroinvertebrates and zooplankton) of glacier retreat in these environments. To assess parallels in biotic responses across streams and lakes, both primary data and findings from other publications were synthesised. Using TITAN (Threshold Indicator Taxa ANalysis) changes in community composition of river taxa were identified at thresholds of <5.1% glacier cover and <66.6% meltwater contribution. Below these thresholds the loss of cold stenothermic benthic invertebrate taxa, Diamesa spp. and the Pyrenean endemic Rhyacophila angelieri was apparent. Some generalist taxa including Protonemura sp., Perla grandis, Baetis alpinus, Rhithrogena loyolaea and Microspectra sp. increased when glacier cover was <2.7% and <52% meltwater. Patterns were not as distinct for the alpine lakes, due to fewer sampling sites; however, Daphnia longispina grp. and the benthic invertebrate groups Plectopera and Planaria were identified as potential indicator taxa. While further work is required to assess potential indicator taxa for alpine lake systems, findings from alpine river systems were consistent between methods for assessing glacier influence (meltwater contribution/glacier cover). Hence, it is clear that TITAN could become a useful management tool, enabling: (i) the identification of taxa particularly sensitive to glacier retreat; and (ii) conservation efforts/resources to be better directed in alpine aquatic systems.

Prevalence and associated risk factors of male erectile dysfunction among patients on hemodialysis and kidney transplant recipients: a cross-sectional survey from Sudan.

Male erectile dysfunction (ED) is an important issue worldwide occurring in 5-69% of men in community-based studies. It is more common in patients with chronic kidney disease (CKD) and those on peritoneal as well as hemodialysis (HD), occurring in more than 80% of patients. In Sudan, there is no previous report on ED among patients with CKD. A cross-sectional study was done to determine the prevalence of ED and its associated risk factors among Sudanese CKD patients on HD and those who underwent renal transplant. This was conducted in Khartoum, Sudan from October 2005 to July 2006 including all married men who were on maintenance HD for more than three months and all married men who had received renal transplantation at least three months earlier. Single, divorced/separated men, those whose wives were living away, those who were bed-bound and those with cognitive impairment were also excluded. After obtaining consent for participation, demographic and clinical data were collected by using anonymous questionnaires and the Arabic version of International Index of Erectile Function (IIEF; the Egyptian version). Patients who did not participate in full and proper manner were considered as "non-responders." A total of 146 patients, 106 HD patients, and 40 renal transplant recipients completed the IIEF questionnaire. Non-responders constituted 43.7% and 54.5% of HD and transplant recipient patients, respectively. Blood samples were taken after completion of the IIEF questionnaire to determine the required investigations. ED prevalence was high among our study patients, 83% among the HD patients and 67.5% among the renal transplant recipients. Univariate analysis showed that there was a trend, although non-significant, of older age being associated with ED in both groups. Similar association was seen in those who were under-dialyzed in the HD group and DM in the transplant recipient group. Previous history of ED was significantly associated with current presence of ED in both groups. More studies with larger sample size are needed to clarify the results of this study.

Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers.

This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0→t, AUC0→∞, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0→t, AUC0→∞ and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent.

Bioequivalence evaluation of 320 mg gemifloxacin tablets in healthy volunteers.

This study was done to compare the bioavailability of a new tablet formulation of gemifloxacin (gemifloxacin 320 mg/tablet) with that of the reference product (factive 320 mg/tablet). The bioequivalence of a single dose (320 mg) was assessed for gemifloxacin included in the test and reference products by comparing the pharmacokinetic parameters derived from the plasma concentration-time profiles following administration to 24 healthy male volunteers in a balanced, 2-period, 2-sequence, 2-way crossover design. Plasma concentrations of gemifloxacin were analyzed by a validated and sensitive HPLC assay developed in-house. The mean plasma concentration-time profiles are almost superimposable. 18 ANOVAs were performed to compare gemifloxacin plasma levels of the two formulations at each sampling time and there were no statistical differences between the two formulations. The parameters used to measure bioavailability were AUC0-t, AUC0-infinity and Cmax and they were calculated by a model-independent method. The parametric 90% confidence intervals of the mean values for the test/reference ratio were in each case well within the bioequivalence acceptable boundaries of 80-125% for AUCo-t, AUC0-infinity and Cmax. Data obtained in this study prove, by appropriate statistical methods, the essential similarity of plasma levels of gemifloxacin from the test product with those from the reference product suggesting equal clinical efficacy of these two products.

Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers.

This investigation was carried out to evaluate the bioavailability of a new suspension formulation of cefixime (100 mg/5 ml), Winex, relative to the reference product, Suprax (100 mg/5 ml) suspension. The bio-availability study was carried out in 24 healthy male volunteers who received a single oral dose (200 mg) of the test (A) and the reference (B) products on 2 treatment days after an overnight fast of at least 10 hours. The treatment periods were separated by a one-week washout period. A randomized, balanced two-way crossover design was used. After dosing, serial blood samples were collected over a period of 16 hours. Plasma concentrations of cefixime were analyzed using a sensitive high-performance liquid chromatographic assay. The pharmacokinetic parameters for cefixime were determined using standard non-compartmental method. The parameters AUC(0-t), AUC(0-infinity), Cmax, Kel, t1/2 and Cmax/AUC(0-infinity) were analyzed statistically using raw and log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pnfinity harmacokinetic parameters: AUC(0-t), AUC(0-infinity) Cmax, and Cmax/AUC(0-infinity) were within the range 80 - 125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax, and Cmax/AUC(0-infinity) were 88.93 - 107.10%, 89.09 - 107.11%, 89.63 - 108.58% and 96.85 - 105.29%, respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), and Cmax using the Schuirmann's two one-sided t-tests. Therefore, the two formulations were considered to be bioequivalent.

Comparative bioavailability study of doxycycline hyclate (equivalent to 100 mg doxycycline) capsules (doxycin vs vibramycin) for bioequivalence evaluation in healthy adult volunteers.

This investigation was carried out to evaluate the bioavailability of a new capsule formulation of doxycycline (100 mg), doxycin, relative to the reference product, vibramycin (100 mg) capsules. The bioavailability was carried out in 24 healthy male volunteers who received a single dose (100 mg) of the test (A) and the reference (B) products after an overnight fast of at least 10 hours on 2 treatment days. The treatment periods were separated by a 2-week washout period. A randomized, balanced 2-way cross-over design was used. After dosing, serial blood samples were collected for a period of 48 hours. Plasma concentrations of doxycycline were analyzed by a sensitive and validated high-performance liquid chromatography assay. The pharmacokinetic parameters for doxycycline were determined using standard noncompartmental methods. The parameters AUC(0-t), AUC(0-infinity), Cmax, K(el), t(1/2) and Cmax/AUC(0-infinity) were analyzed statistically using log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pharmacokinetic parameters: AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were within the range 80-125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis of the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were 95.98-109.56%, 92.21 to 107.66%, 93.90-112.56%, and 96.0 to 106.91% respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) by the Schuirmann's two 1-sided t-tests. Therefore, the 2 formulations were considered to be bioequivalent.

Effect of lamotrigine on the pharmacokinetics of carbamazepine and its active metabolite in dogs.

The effect of lamotrigine (LTG) on the pharmacokinetics of carbamazepine (CBZ) and its active metabolite; carbamazepine-epoxine (CBZ-E), was investigated in dogs. Five male dogs received CBZ (2 x 200 mg tab, p.o.) daily for a period of 1 week. After the end of this period, blood samples were collected serially for up to 24 hrs. After a wash-out period of I week, LTG (100 mg tab, p.o.) was coadministered with the CBZ dose (2 x 200 mg tab, p.o.) for 7 days. Blood samples were again serially collected and plasma levels of CBZ and CBZ-E were analysed by high performance liquid chromatography (HPLC). Concurrent administration of LTG with CBZ did not have any significant effect on the pharmacokinetic parameters of CBZ. There was also no significant difference between the plasma concentration ratio (CBZ-E to CBZ) vs time profiles in the two schedules of drug administration signifying the absence of pharmacokinetic interaction between LTG and CBZ or its active metabolite in this animal model.

Liquid chromatographic assay of nifedipine in human plasma and its application to pharmacokinetic studies.

A highly sensitive, selective and reproducible reversed-phase high-performance liquid chromatographic method has been developed for the determination of nifedipine in human plasma with minimum sample preparation. The method is sensitive to 3 ng/ml in plasma, with acceptable within- and between-day reproducibilities and linearity (r2 > 0.99) over a concentration range from 10-200 ng/ml. Acidified plasma samples were extracted using diethyether containing diazepam as internal standard and chromatographic separation was accomplished on C18 column using a mobile phase consisting of acetonitrile, methanol and water (35:17:48, v/v). The within-day precision ranged from 2.22 to 4.64% and accuracy ranged from 102.4-106.4%. The day-to-day precision ranged from 2.34-7.07% and accuracy from 95.1-100.1%. The relative recoveries of nifedipine from plasma ranged from 91.0-107.3% whereas extraction recoveries were 88.6-93.3%. Following eight 6-week freeze-thaw cycles, nifedipine in plasma samples proved to be stable with accuracy ranging from 0.64 to 3.0% and precision ranging from 3.6 to 4.15%. Nifedipine was also found to be photostable for at least 120 min in plasma, 30 min in blood and for 60 min in aqueous solutions after exposure to light. The method is sensitive and reliable for pharmacokinetic studies and therapeutic drug monitoring of nifedipine in humans after the oral administration of immediate-release capsules and sustained-release tablets to five healthy subjects.

Bioequivalence evaluation of norfloxacin 400 mg tablets (Uroxin and Noroxin) in healthy human volunteers.

A bioequivalence study of two oral formulations of 400 mg norfloxacin was carried out in 18 healthy volunteers according to a single dose, two-sequence, cross-over randomized design at College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, jointly with King Khalid University Hospital. The two formulations were: Uroxin (Julphar, United Arab Emirates) as test and Noroxin (Merck Sharpe & Dohme, BV, Netherlands). Both test and reference formulations were administered to each subject after an overnight fasting on 2 treatment days separated by 1 week wash-out period. After dosing, serial blood samples were collected for a period of 24 h. Plasma harvested from blood, was analysed for norfloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2), and K(el) were determined from plasma concentrations for both the formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-infinity), and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval for test/reference ratio of these parameters were found within a bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Uroxin is bioequivalent to Noroxin.

Bioequivalence evaluation of two brands of cefuroxime 500 mg tablets (Cefuzime and Zinnat) in healthy human volunteers.

A bioequivalence study of two oral formulations of 500 mg cefuroxime axetil was carried out in 24 healthy volunteers following a single dose, standard two-treatment cross-over design at the College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, working jointly with King Khalid University Hospital. The two formulations used were Cefuzime (Julphar, United Arab Emirates) as the test and Zinnat (Glaxo Wellcome, England) as the reference product. Both test and reference tablets were administered to each subject after an overnight fasting on two treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 8 h. Plasma harvested from blood was analysed for cefuroxime by a sensitive, reproducible and accurate high pressure liquid chromatography (HPLC) method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2) and K(el) were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on an analysis of variance (ANOVA); 90% confidence interval for test/reference ratio of these parameters were found within bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Cefuzime is bioequivalent to Zinnat.

Phenytoin dosage adjustment in Saudi epileptics: utilization of steady-state pharmacokinetic parameters.

We determined the Michaelis-Menten parameters (Vmax and Km) in 271 Saudi epileptic patients having generalized tonic-clonic seizures and who were treated with phenytoin (PHT) using high pressure liquid chromatography (HPLC). The patients comprised 150 (55.4%) males and 121 (44.6%) females, with a mean age of 31.7 years (SD = 18.5). The mean Vmax for subjects less than 16 years of age was 10.35 mg/kg/day (SD = 0.73, range = 3.77-17.01), while for those above 16 years, the mean value was 7.99 mg/kg/day (SD = 0.15, range = 3.68-15.95). The difference was statistically significant (P < 0.001). Vmax was positively correlated with weight (r = 0.953), but negative with age (r = -0.903). Km values ranged from 1.01-20.87 mg/litre. The adult Km mean of 6.52 mg/l (SD = 0.24) was significantly higher than the mean of 4.79 mg/l (SD = 0.40) for pediatric patients (P < 0.01), but Km was correlated neither with age nor with weight. Our results showed no difference between the predicted and observed serum PHT concentrations in both the pediatric and adult patients when the respective age group Km and Vmax values were used to adjust PHT doses. The pediatric cases, however, required 30% more PHT per kilogram of body weight than the adults for the achievement of similar serum concentrations.

Bioequivalence evaluation of lomefloxacin 400 mg tablets (Lomax versus Maxaquin in healthy human volunteers.

This study represents the results of a randomized, single dose, two-treatment, two-period crossover study in 18 healthy male volunteers to assess the bioequivalence of two tablets of 400 mg lomefloxacin. The two formulations were: Lomax(R) (Julphar, United Arab Emirates) as the test formulation and Maxaquin(R) (Searle, S.A., UK) as the reference formulation. The study was conducted at the College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, jointly with King Khalid University Hospital, Riyadh, Saudi Arabia. After overnight fasting the two products were administered as a single dose on two treatment days separated by a 1 week washout period. Serial blood samples were collected thereafter, for a period of 48 h. Plasma harvested from blood was analysed for lomefloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max,) T(max), T(1/2), K(elm) and C(max)/AUC(0-infinity) were determined from plasma concentrations for both formulations and found to be in good agreement with reported values. Statistical modules applied to AUC(0-t), AUC(0-infinity) and C(max) revealed no significant difference in the two tested products. Based on these statistical inferences it was concluded that Lomax(R) is bioequivalent to Maxaquin(R).

High-performance liquid chromatographic determination of furosemide in plasma and urine and its use in bioavailability studies.

A sensitive, selective and efficient reversed-phase high-performance liquid chromatographic (HPLC) method is reported for the determination of furosemide in human plasma and urine. The method has a sensitivity limit of 5 ng/ml in plasma, with acceptable within- and between-day reproducibilities and good linearity (r2>0.99) over a concentration range from 0.05 to 2.00 microg/ml. The one-step extract of furosemide and the internal standard (warfarin) from acidified plasma or urine was eluted through a muBondapak C18 column with a mobile phase composed of 0.01 M potassium dihydrogenphosphate and acetonitrile (62:38, v/v) adjusted to pH 3.0. Within-day coefficients of variation (C.V.s) ranged from 1.08 to 8.63% for plasma and from 2.52 to 3.10% for urine, whereas between-day C.V.s ranged from 4.25 to 10.77% for plasma and from 5.15 to 6.81% for urine at three different concentrations. The minimum quantifiable concentration of furosemide was determined to be 5 ng/ml. The HPLC method described has the capability of rapid and reproducible measurement of low levels of furosemide in small amounts of plasma and urine. This method was utilized in bioavailability/pharmacokinetic studies for the routine monitoring of furosemide levels in adults, children and neonate patients.

Comparative bioavailability of two tablet formulations of ranitidine hydrochloride in healthy volunteers.

This investigation was carried out to evaluate the bioavailability of a new tablet formulation of ranitidine HCl (300 mg), Ranid, relative to the reference product, Zantac, (300 mg) tablets. The bioavailability was carried out on 24 healthy male volunteers who received a single dose (300 mg) of the test (T) and the reference (R) products in the fasting state, in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 16 hours. Plasma harvested from blood was analyzed for ranitidine by a sensitive and validated high-performance liquid chromatographic assay. The maximum plasma concentration (Cmax), area under the plasma concentration time curve up to the last measurable concentration (AUC0-t), and to infinity (AUC0-infinity) and the absorption rate (Cmax/AUC0-infinity) were analyzed statistically under the assumption of a multiplicative model. The time to maximum concentration (Tmax) was analyzed assuming an additive model. The parametric confidence intervals (90%) of the mean values of the pharmacokinetic characteristics (AUC0-t, AUC0-infinity), Cmax and Cmax/AUC0-infinity) for T/R ratio were in each case well within the bioequivalence acceptable range of 80-125%. The test formulation was found bioequivalent to the reference formulation by the Schuirmann's two one-sided t-tests and by Wilcoxon Mann Whitney two one-sided tests procedure. Therefore, the 2 formulations were considered to be bioequivalent.

Comparative bioavailability of two tablet formulations of acyclovir in healthy volunteers.

This investigation was carried out to evaluate the bioavailability of a new tablet formulation of acyclovir (400 mg), Clovir, relative to reference product, Zovirax (400 mg) tablets. The 2 brands were found to be similar in weight variation, disintegration time, dissolution, and assay as stipulated by the USPXXIII, as well as by the manufacturer. The bioavailability was carried out on 24 healthy male volunteers who received a single dose (400 mg) of the test (T) and the reference (R) products in the fasting state, in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 16 hours. Plasma harvested from blood was analyzed for acyclovir by a sensitive and validated high-performance liquid chromatographic assay. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve up to the last measurable concentration (AUC0-t), and to infinity (AUC0-infinity), and the absorption rate (Cmax/AUC0-infinity) were analyzed statistically under the assumption of a multiplicative model. The time to maximum concentration (Tmax) was analyzed assuming an additive model. The parametric confidence intervals (90%) of the mean values of the pharmacokinetic characteristics (AUC0-t, AUC0-infinity, Cmax, Cmax/AUC0-infinity) for T/R ratio were in each case, well within the bioequivalence acceptable range of 80-125%. The test formulation was found bioequivalent to the reference formulation by the Schuirmann's two 1-sided t tests and by Wilcoxon Mann Whitney two 1-sided tests procedure. Therefore, the 2 formulations were considered to be bioequivalent.

Myofibroblastoma: an unusual breast lump.

A case of myofibroblastoma of the breast is reported. The clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm.

Determination of pefloxacin and its main active metabolite in human serum by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method is described for the simultaneous determination of a fluoroquinolone, pefloxacin, and its main active metabolite norfloxacin (N-desmethyl metabolite) in serum. Sample preparation involves protein precipitation with acetonitrile. The drugs and the internal standard (acebutolol) were eluted from a 4-microns Novapak C-18 cartridge at ambient temperature with an isocratic mobile phase consisting of 14% acetonitrile in buffer solution, at a flow rate of 2.5 ml/min. The effluent was monitored on a fluorescence detector using excitation and emission wave-lengths of 330 and 440 nm, respectively. Each analysis required no longer than 8 min. Quantification was achieved by measurement of the peak-area ratio of the drugs to the internal standard, and the limit of quantification for both pefloxacin and norfloxacin in serum was 50 ng/ml. The intraday coefficient of variation (CV) ranged from 1.3 to 4.4% and from 2.2 to 7.5% for pefloxacin and norfloxacin, respectively, at the concentration ranges evaluated. The interday CV ranged from 1.1 to 5.9% and from 2.3 to 5.6% for pefloxacin and norfloxacin, respectively, at three concentrations. Relative recovery was 105.5 and 99.5% for pefloxacin and norfloxacin, respectively. Stability tests show that pefloxacin and norfloxacin are stable in serum for at least 3 weeks when stored at -20 degrees C. This method has been used successfully in pharmacokinetic studies in humans.