Alfred E Staubus

• Pharm.D., Ph.D.
• Emeritus at The Ohio State University

The pharmacokinetics of sodium borocaptate ( BSH), a drug that has been used clinically for boron neutron capture therapy ( BNCT) of malignant brain tumors, have been characterized by measuring boron concentrations by direct current plasma- atomic emission spectroscopy ( DCP- AES) in a group of 23 patients with high- grade gliomas. The disposition...

The pharmacokinetics of sodium borocaptate (BSH), a drug that has been used clinically for boron neutron capture therapy (BNCT) of malignant brain tumors, have been characterized by measuring boron concentrations by direct current plasma-atomic emission spectroscopy (DCP-AES) in a group of 23 patients with high-grade gliomas. The disposition of BSH...

We have developed a quantitative assay using electrospray ionization mass spectrometry coupled to reversed-phase ion-pair liquid chromatography (LC/MS) for quantitation of sodium borocaptate (BSH) in human plasma. The assay was developed using a Micromass Q-TOF II mass spectrometer equipped with an orthogonal electrospray source. The mobile phase w...

Boron neutron capture therapy (BNCT) is based on a nuclear capture reaction that occurs when boron-10, a stable isotope, is irradiated with low energy neutrons to produce high-energy alpha particles and recoiling lithium-7 nuclei. The purpose of the present study was to determine what urinary metabolites, if any, could be detected in patients with...

To report a case of valproic acid overdose treated successfully with high-flux hemodialysis without the addition of charcoal hemoperfusion. A 25-year-old white woman with a history of multiple suicide attempts and schizophrenia presented after ingesting an unknown amount of valproic acid. She became comatose and developed hypotension and lactic aci...

The purpose of this study was to obtain tumor and normal brain tissue biodistribution data and pharmacokinetic profiles for sodium borocaptate (Na2B12H11SH) (BSH), a drug that has been used clinically in Europe and Japan for boron neutron capture therapy of brain tumors. The study was performed with a group of 25 patients who had preoperative diagn...

OBJECTIVE: The purpose of this study was to obtain tumor and normal brain tissue biodistribution data and pharmacokinetic profiles for sodium borocaptate (Na2B12H11SH) (BSH), a drug that has been used clinically in Europe and Japan for boron neutron capture therapy of brain tumors. The study was performed with a group of 25 patients who had preoper...

Dietary uptake efficiency (α) and elimination rate constants (kd) of 2,2ǐ,4,4ǐ,5,5ǐ-hexachlorobiphenyl (HCBP) were determined in two fish species, yellow perch and rainbow trout, to investigate the influence of dietary and body lipid levels on bioaccumulation. Groups of juvenile fish with significant differences in percent body lipid were fed with...

Dietary uptake efficiency (α) and elimination rate constants (k(d)) of 2,2',4,4',5,5'-hexachlorobiphenyl (HCBP) were determined in two fish species, yellow perch and rainbow trout, to investigate the influence of dietary and body lipid levels on bioaccumulation. Groups of juvenile fish with significant differences in percent body lipid were fed wit...

Dietary uptake efficiency (α) and eliminate rate constants (k{sub d}) of 2,2â²,4,4â²,5,5â²-hexachlorobiphenyl (HCBP) were determined in two fish species, yellow perch and rainbow trout, to investigate the influence of dietary and body lipid levels on bioaccumulation. Groups of juvenile fish with significant differences in percent body lipid were f...

Pilocarpine hydrochloride suspended in a candy-like pastille was evaluated as a topical treatment for radiation-induced xerostomia in head and neck cancer patients. This local delivery system, which differs from systemically administered pilocarpine preparations, was developed to hopefully maximize the local response and minimize the systemic side...

Goups of juvenile channel catfish (Ictalurus punctatus) were exposed for 10 days to control or contaminated sediment, spiked with 14C-hexachlorobiphenyl (HCBP, 130 μg·kg−1 dry weight), in order to establish a known body burden. At the completion of that exposure, subsamples offish were taken for HCBP analysis and the remaining fish were transferred...

The Radioimmunoguided Surgery (RIGS) system was developed, in part, to detect occult tumor in patients with recurrent colorectal cancer. Unfortunately, however, patients are sometimes found to have unresectable peritoneal metastasis. For these patients, intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) was used as a novel treatme...

Intraperitoneal (i.p.) metastases pose a special problem for surgical treatment because of their multiplicity and microscopic size. This study was designed to examine the feasibility and safety of i.p. hyperthermic perfusion (IPHP) with mitomycin C (MMC) for treating recurrent colorectal cancer. Fifteen patients with metastatic colon cancer were tr...

Sodium borocaptate (Na2B12H11SH, designated as “BSH”) has been used clinically in Japan for over 25 years by Hatanaka et al. as a capture agent for boron neutron capture therapy (BNCT) of brain tumors.1 Independently, p — boronophenylalanine (BPA), which originally had been synthesized by Snyder2, has been used clinically by Mishima et al. as a cap...

The present study was carried out to determine the efficacy of Boron Neutron Capture Therapy (BNCT) for intracerebral melanoma using nude rats, the human melanoma cell line MRA 27, and boronophenylalanine as the capture agent. Pharmacokinetic and tissue distribution studies: MRA 27 cells (2 x 10(5)) were implanted intracerebrally, and 30 days later...

A two compartment pharmacokinetic model was developed which describes the uptake and elimination of 5,5,6-trichlorobiphenyl (TCB) and pentachlorophenol (PCP) in the midge, Chironomus riparius. C. riparius were exposed to nominal TCB (2 g L–1) and PCP (9 g L–1) concentrations during a 16 h static uptake phase. Depuration was determined over approxim...

The purpose of the present study was to determine the efficacy of boron neutron capture therapy (BNCT) in treating the therapeutically refractory F98 glioma, using boronophenylalanine (BPA) as the capture agent. F98 glioma cells (10(5)) were implanted stereotactically into the brains of Fischer rats and 15 days later the animals were injected intra...

A rat brain tumor model has been developed utilizing nude rats and the human melanoma cell line MRA 27. For pharmacokinetic and tissue distribution studies, 2 10(5) MRA 27 cells were implanted intracerebrally (i.c.), and 30 days later, 120 mg of 10B-enriched L-boronophenylalanine were injected i.p. into nude rats. 10B concentrations in the tumor, b...

Malignant melanoma is a highly metastatic tumor to the skin, liver, lung and especially the brain. Patients with brain metastases have a poor prognosis despite aggressive chemo-and radiotherapy. Many of these patients have disseminated melanoma but eventually succumb to their cerebral metastatic disease.

Para-boronophenylalanine (BPA) has been used as a boron delivery agent for boron neutron capture therapy (BNCT) of melanoma1. As an analogue of phenylalanine, a melanin precursor, it has been postulated that melanoma cells selectively take up BPA. The effectiveness of BNCT is dependent, in part, upon the concentration gradient of boron in the tumor...

Fifty percent of primary malignancies of the central nervous system are anaplastic astrocytomas and glioblastoma multiforme1. The prognosis of patients with these tumors is dismal despite aggressive surgery followed by radio-and chemotherapy, and characteristically the mean survival time of these patients still is approximately 12 months2,3.

Melanoma metastatic to the brain is a serious clinical problem for which there currently is no satisfactory treatment. Boron neutron capture therapy (BNCT) has been shown by Mishima et al. to be clinically effective in the treatment of cutaneous melanoma using ¹°B-enriched boronophenylalaine (BPA) as the capture agent. In the present pilot study...

Melanoma metastatic to the brain is a serious clinical problem for which there currently is no satisfactory treatment1,2. Boron neutron capture therapy (BNCT) has been shown by Mishima et al. to be clinically effective in the treatment of cutaneous melanoma using 10B-enriched boronophenylalaine (BPA) as the capture agent3. Similarly, Coderre et al....

Fludara I.V. (fludarabine phosphate) (2-F-ara-adenosine monophosphate [2-F-ara-AMP], NSC 312887) is the 5'-phosphate of 2-F-ara-A-(9-beta-D-arabinofuranosyl-2-fluoroadenine), a derivative of ara-A that is resistant to deamination and selectively inhibits DNA synthesis. Concurrent with the phase I evaluation of 2-F-ara-AMP administered as a single i...

The purpose of the present study was to utilize a well-established rat glioma to evaluate boron neutron capture therapy for the treatment of malignant brain tumors. Boron-10 (10B) is a stable isotope which, when irradiated with thermal neutrons, produces a capture reaction yielding high linear energy transfer particles (10B + 1nth----[11B]----4He(a...

We have investigated the ability of 99Tcm-disofenin (DISIDA) kinetics to measure liver function. Two approaches have been used: first, quantitative analysis of serial liver images, and second, clearance estimation from whole blood concentration-time data. Graded liver dysfunction was produced in 11 dogs over three months by common bile duct ligatio...

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with thermal neutrons to yield stripped down helium nuclei (alpha particles) and recoiling lithium-7 nuclei.1

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) have been studied in dogs. Serial blood sampling permitted calculation of whole blood disposition rates, which principally represent liver clearance. There were striking differences in these rates between 6 normals and 7 animals in whom liver damage was induced...

The limited sampling model (LSM) offers a means of estimating the area under the concentration-time curve (AUC) from only two timed plasma concentrations. In this study, pharmacokinetic profiles were simulated for 23 patients treated with amonafide, using each patient's individual pharmacokinetic parameters. Data were simulated for a dose of 250 mg...

Fludarabine phosphate was studied in a phase I trial of a loading dose/continuous-infusion schedule. The schedule was chosen to rapidly achieve and maintain concentrations that have been shown in vitro to achieve maximal inhibition of cell growth. The initial level was a loading dose of 20 mg/m2 followed by a 48-hour continuous iv (CIV) infusion of...

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) have been studied in dogs. Serial blood sampling permitted calculation of whole blood disposition rates, which principally represent liver clearance. There were striking differences in these rates between 6 normals and 7 animals in whom liver damage was induced...

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) has been studied in normal subjects and patients with documented liver disease. The apparent overall whole blood disposition rates of radioactivity were calculated from serial blood data, in order to evaluate liver clearance of DISIDA. The measurements obtained...

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) has been studied in normal human subjects and patients with documented liver disease. The apparent overall whole blood disposition rates of radioactivity were calculated from serial blood data, in order to evaluate liver clearance of DISIDA. The measurements obt...

A new method for calculation of the apparent absorption rate constant of a drug has been derived based on the relationship between the plasma concentrations after an oral dose and the area intervals under both the oral and the intravenous plasma concentration–time curves. The method is a noncompartmental technique evolved from the convolution integ...

Total parenteral nutrition (TPN) is thought to induce cholestasis. However, serum hepatic enzyme abnormalities were found in 70 percent of patients before TPN was started. Rate constants (alpha, beta, K(E] and total clearance (CIT) of sodium taurocholate (STC) and indocyanine green (ICG) were studied in 20 carefully selected patients not on TPN and...

The pharmacokinetics and metabolism of 8-methoxypsoralen (8-MOP) were measured in the catheterized rat after a single i.v. dose. Blood samples were collected serially and analyzed using a sensitive and specific assay for [14C]-8-MOP. Total body clearance of 8-MOP was 7.3, 3.9, 1.7, 1.0, 0.78 and 0.42 liters/kg/hr at doses of 0.2, 1.0, 2.5, 5.0, 10...

Following intravenous infusion with approximately 300 mg deuterium oxide per kg body weight, blood was drawn from lactating Holsteins (Trial 1, n = 4, and Trial 2, n = 5) at suitable intervals for up to 12 days while the cows were maintained on dietary regimens to which they were well adapted. Time results for deuterium oxide concentration in blood...

Body composition was studied in five animal groups (two 8-week-old calves, two 16-week-old calves, three Holsteins and three Jerseys in late lactation and two groups of cows each having a Holstein and a Jersey in early lactation). Each group was fed a different diet so as to effect wide variations in body composition. Body water volume and kinetics...

Organ distribution and blood concentration profiles were compared following injection of mice with radiolabeled test agents via the lateral tail vein or retroorbital venous sinus. Monoclonal antibodies directed against B16 melanoma of C57BL/6 origin were labeled with iodine-125. Thymocytes from BALB/c mice and B16 melanoma cells were labeled with t...

An analytical method for determination of 2'-deoxycoformycin (2'-DCF) concentrations in plasma and urine was developed based upon a modification of adenosine deaminase (ADA) inhibition assays described in the literature. The method involves the spectrophotometric monitoring of the rate of deamination of adenosine by the enzyme in the presence of va...

The pharmacokinetics and metabolism of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) have been examined in the mouse, rat, rabbit, and dog using tritiated drug as a marker. In all four species, tiazofurin, given as a single bolus iv injection, is removed from the circulation in a triphasic manner, with a generally prolonged terminal hal...

In contrast to first-order elimination systems, time-averaged clearance (Dose/AUC0→∞) in Michaelis-Menten elimination systems is considered to be meaningless since the instantaneous clearance [Vmax/(Km + Cp)] in such systems changes as a function of time and concentration. The mean residence time is also not considered to be meaningful in Michaelis...

Naltrexone release rates from a controlled release delivery system have been quantitated over a time period greater than one month in the monkey. The method requires calibration of the pharmacokinetic parameters of each monkey utilizing an intravenous bolus dose and assay of unchanged naltrexone levels in plasma as a function of time after dosing....

An HPLC analytical method was applied to the determination of plasma concentrations of 5,6-dihydro-5-azacytidine (NSC 264880, DHAC) in two foxhounds after a rapid intravenous infusion of 300 mg/kg DHAC. The dose employed is the mouse equivalent LD10 dose which results in mild reversible toxicity in the dog. The decline in DHAC plasma concentrations...

Iopanoic acid was used as a model compound to study the effect of the intestinal perfusion rate on the mean absorption clearance. Absorption of iopanoic acid followed first-order kinetics, with a first-order absorption rate constant (ka) linearly dependent on the dry intestinal weight. An absorption clearance--time plot revealed three phases. Phase...

A method designed to quantitate in vivo naltrexone release rates from sustained-release systems has been applied to the evaluation of seven different naltrexone delivery systems in the monkey. The method consists of two phases: a single intravenous bolus dose quantitation of each monkey's pharmacokinetic parameters coupled with a delivery system st...

The field of radiology in general, and gastrointestinal radiology in particular, can and has benefited by the application of pharmacokinetic principles in contrast agent research and development. The application of basic pharmacokinetic principles can aid in the design of new synthetic analogues. In many cases, the presence or the absence of certai...

2,3-Dihydro-1H-imidazo[1,2-b]pyrazole (IMPY) is an inhibitor of ribonucleotide reductase and of DNA synthesis selected for clinical trials because of its activity against L1210 leukemia variants resistant to other inhibitors of this enzyme. A phase I trial designated to allow in-depth pharmacologic evaluation has recently been completed and the cli...

Oily iodinated organic carbonates were investigated for use as myelographic media. The urinary excretion of total iodine was used to monitor the apparent elimination rate of these compounds from the subarachnoid space. Within the chain length series of C2-C6, the decrease of elimination rates and disposition rate constants with increasing chain len...

This investigation generated data characterize a specific electron-capture GLC assay reported previously for naltrexone and applied the method to a determination of naltrexone pharmacokinetics. Extraction efficiencies are reported for the assay, and mass spectral evidence indicates that naltrexone forms a triester when derivatized for electron-capt...

Cytembena is a nonmyelosuppressive drug that has received phase I--II trials in this country and is presently being used as a chemotherapeutic agent in Europe. Sterile abscesses at the site of im injection and "autonomic storm" after iv bolus represent the most frequent dose-limiting toxic effects, and intermittent schedules reflect reports of prol...

The biliary excretion of two oral cholecystographic contrast agents, iocetamic acid and iopanoic acid, were compared during low and high taurocholate infusion rates. The pharmacokinetics of these compounds after intravenous infusion were studied in bile-fistula dogs using both indirect and direct pharmacokinetic techniques. The indirect multiple in...

The main metabolites of the narcotic antagonist naltrexone (NTX) have been isolated and identified by several research groups. The purpose of this study was to elucidate the plasma kinetics of NTX and its glucuronide metabolite(s) (NTX-G) in the dog. NTX (0.8 mg/kg) was administered by iv bolus and plasma samples were obtained over the next 7 hr an...

Capacity-limited elimination of sodium iopanoate and a reproducible apparent transport maximum (Tm) were demonstrated in nonoperated dogs having an intact enterohepatic circulation and normal endogenous bile salt pool. Using a multiple infusion technique, estimation of apparent Tm of iopanoate in the liver was possible without sampling either bile...

Experiments were carried out in dogs with a modified Thomas cannula in the duodenum through which the common bile duct could be catheterized. Constant intravenous infusion of sodium iopanoate at different infusion rates greater than the apparent excretion maximum revealed linearity of the blood concentration with time above a threshold concentratio...

Excretion studies on sodium tyropanoate (Bilopaque sodium) were perfomed on dogs having a modified Thomas cannula in the duodenum opposite the ampulla of Vater. The data from these studies were compared with those from earlier studies previously performed in the same dogs with sodium iopanoate (sodium salt of Telepaque). Although we found the gross...