Robert Baughman

Robert Baughman

PharmD, PhD

About

73
Publications
2,930
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,887
Citations
Citations since 2017
11 Research Items
245 Citations
2017201820192020202120222023010203040
2017201820192020202120222023010203040
2017201820192020202120222023010203040
2017201820192020202120222023010203040
Introduction
Robert Baughman currently works as a consultant in pharmaceutical drug development. Robert's research has focused on Gastric Disease and Diabetology. His most recent publication is 'Supplementary Material 4'.
Skills and Expertise

Publications

Publications (73)
Article
Full-text available
Background This study was performed to satisfy a US Food and Drug Administration post-marketing requirement to compare the dose responses for Technosphere® Insulin (TI; MannKind Corporation, Westlake Village, CA, USA) and subcutaneous insulin lispro (LIS) across a wide range of doses.Objectives This single-center, open-label, randomized, cross-over...
Article
Full-text available
Technosphere insulin (TI), an inhaled insulin with a fast onset of action, provides a novel option for the control of prandial glucose. A euglycemic glucose clamp study was performed to compare the effects of TI and regular human insulin (RHI) on the induced glucose infusion rate (GIR) in healthy volunteers. Generation of a dose-response relationsh...
Data
Supplemental Figure 2: The result of the profiling to identify a value for GIRmax is shown. The starting value of 14.4 mg/kg/min has been taken from reference [8], while the minimum was found to be 11.9 mg/kg/min for the given data set.
Data
Supplementary Table 1 Population Pharmacokinetic parameters of Insulin
Data
Supplemental Figure 3: Visual Predictive Check of the Pharmacokinetic‐GIR Model. Checks are prediction corrected. Figure B corresponds to RHI (15IU), all other figures to inhaled TI (A: 10U TI, C: 30U TI, D: 60U TI, E: 80U TI).
Data
Supplementary Table 2 Parameters describing the onset and duration of action derived from the GIRAUC,0‐20h time profiles
Data
Supplemental Figure 1: Visual Predictive Check of the Pharmacokinetic Model. Checks are prediction corrected. Figure B corresponds to RHI (15IU), all other figures to inhaled TI (A: 10U TI, C: 30U TI, D: 60U TI, E: 80U TI).
Data
Supplementary Figure 4: Visual Predictive Check of the Dose GIRAUC Model. Checks are prediction corrected. Figure A shows inhaled TI, B corresponds to RHI.
Article
Advances in insulin treatment options over recent decades have markedly improved the management of diabetes. Despite this, glycemic control remains suboptimal in many people with diabetes. Although postprandial glucose control has been improved with the development of subcutaneously injected rapid-acting insulin analogs, currently available insulin...
Article
Full-text available
To investigate the efficacy and safety of prandial Technosphere inhaled insulin (TI), an inhaled insulin with a distinct time action profile, in insulin-naïve type 2 diabetes (T2D) inadequately controlled on oral antidiabetes agents (OADs). Subjects with T2D with HbA1c levels ≥7.5% (58.5 mmol/mol) and ≤10.0% (86.0 mmol/mol) on metformin alone or tw...
Article
ROSE-010, a Glucagon-Like Peptide-1 (GLP-1) analog, reduces gastrointestinal motility and relieves acute pain in patients with irritable bowel syndrome (IBS). The rat small bowel migrating myoelectric complex (MMC) is a reliable model of pharmacological effects on gastrointestinal motility. Accordingly, we investigated whether ROSE-010 works throug...
Article
Historically, quantitative clinical diagnostic assays (QCDAs) have not been accepted for use in pharmacokinetic or bioequivalence studies because they do not fully comply with the US Food and Drug Administration (FDA) Guidance for Industry: Bioanalytical Method Validation (e.g., full calibration curve not generated with each analytical run). Sample...
Article
To determine distribution and deposition of Technosphere® Insulin (TI) inhalation powder and the rate of clearance of fumaryl diketopiperazine (FDKP; major component of Technosphere particles) and insulin from the lungs. Deposition and distribution of (99m)pertechnetate adsorbed onto TI immediately after administration using the MedTone® inhaler wa...
Article
Insulin exposure after inhalation has been reported to be altered significantly in subjects with chronic obstructive pulmonary disease (COPD). In this study, the rate and extent of insulin exposure was compared in healthy volunteers and subjects with COPD following administration of Technosphere * Insulin (TI), a dry powder insulin formulation for...
Article
The clinical assessment of new formulations of human insulin is problematic due to the inability to distinguish between endogenous insulin and exogenously administered insulin. The usual methods to surmount the problem of distinguishing between endogenous and exogenous human insulin include evaluation in subjects with no or little endogenous insuli...
Article
Multiple-compartment disposition of insulin has been demonstrated following intravenous administration; however, because of slow absorption and flip-flop kinetics, meal-time insulin pharmacokinetics have been described by a 1-compartment model. Technosphere insulin (TI) is an inhaled human insulin with rapid absorption and a distinct second compart...
Article
Technosphere® [Bis-3,6(4-fumarylaminobutyl)-2,5-diketopiperazine (FDKP)] microparticles, the integral component of the Technosphere inhalation system, deliver drugs to the deep lung and have been used to administer insulin and glucagon-like peptide-1 via inhalation in clinical studies. Three studies were conducted to characterize FDKP pharmacokinet...
Article
Full-text available
MKC253 is glucagon-like peptide 1 (GLP-1, 7-36 amide) adsorbed onto Technosphere microparticles for oral inhalation. The pharmacokinetics of inhaled GLP-1 and the pharmacokinetic-pharmacodynamic (PK-PD) relationship between inhaled GLP-1 and insulin were analyzed in two trials, one in healthy normal volunteers and the other in patients with type 2...
Article
Background: Unfractionated heparin (UFH) is safe and effective for thromboprophylaxis, but its use is limited to parenteral administration. A novel drug delivery agent (SNAC) has been developed to accomplish the oral delivery of heparin. Objective: This report describes the foundation for dose selection and use of oral heparin/SNAC in patients u...
Article
Parenteral low molecular weight heparin (LMWH) is the standard of care for the prevention of deep vein thrombosis in patients undergoing joint replacement or abdominal surgery. LMWH is not absorbed after oral dosing. This article describes the delivery agent-mediated transport of LMWH across Caco-2 cells. These agents are shown to facilitate oral L...
Article
Parathyroid hormone (PTH), the only drug known to stimulate bone formation. is a peptide therapeutic indicated in the treatment of osteoporosis. Unfortunately, PTH is only effective when dosed by injection because it has no oral bioavailability. Herein we report the oral absorption of PTH in rats and monkeys facilitated by the novel delivery agent,...
Article
Heparin is the anticoagulant of choice for hospitalized patients, but it is dosed only by injection because it is not absorbed following oral administration. We have discovered and prepared compounds (delivery agents) that facilitate the gastrointestinal absorption of heparin in rats, monkeys, and humans when given orally. We are currently developi...
Article
Orally administered heparin (OHEP) is unreliable because of poor absorption. Sodium N-(8[2-hydroxybenzoyl]amino) caprylate (SNAC) is an amido acid that facilitates the gastrointestinal absorption of heparin. We evaluated the effectiveness of OHEP combined with SNAC (OHEP/SNAC) in the treatment of deep-vein thrombosis (DVT). An internal jugular DVT...
Article
This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. Forty female pigs were equally assigned to four groups: control (...
Article
During the past decade, dramatic progress in the field of biotechnology has resulted in a large increase in the number of commercially available macromolecular drugs that require parenteral dosing. These new drugs have enormous therapeutic potential, but their use is often limited by their invasive route of administration and with it the complicati...
Article
Sodium N-[10-(2-hydroxybenzoyl)amino]decanoate (SNAD) is a novel carrier that allows the gastrointestinal absorption of low-molecular weight heparin (LMWH). The purpose of this experiment was to evaluate oral LMWH with SNAD for the prevention of deep venous thrombosis. Sixty Sprague-Dawley rats were equally assigned to five experimental groups: gro...
Article
Background: Parenteral heparin is the anticoagulant of choice in hospitalized patients. Continued anticoagulation is achieved by subcutaneous administration of low-molecular-weight heparin or with an orally active anticoagulant such as warfarin. An oral heparin formulation would avoid the inconvenience of subcutaneous injection and the unfavorable...
Article
Sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) is an acetylated amino acid molecule that facilitates the gastrointestinal absorption of heparin. This study was undertaken to evaluate the efficacy of orally administered combination SNAC:heparin in preventing deep venous thrombosis in a standard rat model. Forty-four adult male Sprague-Dawley...
Article
A family of novel compounds (delivery agents) that promote the gastrointestinal absorption of USP heparin in rats and primates has been discovered. The delivery agents in combination with heparin were administered either orally or intracolonically in an aqueous propylene glycol solution and caused dramatic increases in both plasma heparin concentra...
Article
Ten N-acylated, non-alpha-amino acids have been prepared as oral delivery agents and used to demonstrate the oral delivery of heparin in vivo in rats and primates. Following the oral administration of solutions containing a combination of heparin and a delivery agent to rats or primates, significant plasma heparin concentrations were evidenced by A...
Article
A series of N-acetylated, non-alpha, aromatic amino acids was prepared and shown to promote the absorption of recombinant human growth hormone (rhGH) from the gastrointestinal tract. Seventy compounds in this family were tested in vivo in rats. Of the compounds tested, 4-[4-[(2-hydroxybenzoyl)amino]phenyl]butyric acid was identified as a preclinica...
Article
Herein we report the discovery of a group of derivatized alpha-amino acids that increase the oral bioavailability of sodium cromolyn. We prepared three N-acylated alpha-amino acids and used these compounds to demonstrate the oral delivery of cromolyn in an in vivo rat model. In vitro experiments, including permeation studies and near infrared spect...
Article
New approaches to vaccine development have become possible since a common mucosal defense system was recognized whereby an antigen interacting with localized lymphoid tissue could stimulate IgA precursor cells that may then migrate to other mucosal surfaces (Craig and Cebra, 1971). Several oral vaccines have been shown to induce IgA responses at mu...
Article
Drug-loaded proteinoid microspheres were freeze-dried to facilitate shipping and handling and to enable long term storage. Heparin was chosen as the model drug in developing the optimum lyophilization process. The factors influencing the integrity of either heparin-loaded or unloaded ('empty') proteinoid microspheres during freeze-drying were deter...
Chapter
The blood coagulation pathway consists of a series of inactive and active enzymes (Fig. 1). In certain individuals, some of the elements, or factors, of this cascade may be inoperative or have reduced activity, and in some cases may be missing. Such cases give rise to the bleeding disorder hemophilia. There are three categories of patients with the...
Article
The effect of intrathecal tissue plasminogen activator administered at times from 0 to 72 hours after subarachnoid hemorrhage on the development of cerebral vasospasm in primates was examined. Thirty monkeys were randomly assigned into one of five equal groups: a control group that underwent subarachnoid hemorrhage alone, and 0-, 24-, 48-, and 72-h...
Article
Substance P induced a dose-dependent contraction of iris sphincter muscles when applied in the presence of atropine to the isolated rabbit iris in vitro as evidenced by a decreased pupil diameter. Pretreatment of the iris with 20 micrograms of recombinant enkephalinase (neutral endopeptidase; EC 3.4.24.11) totally abolished the contractile response...
Article
: The effect of intrathecal tissue plasminogen activator administered at times from 0 to 72 hours after subarachnoid hemorrhage on the development of cerebral vasospasm in primates was examined. Thirty monkeys were randomly assigned into one of five equal groups: a control group that underwent subarachnoid hemorrhage alone, and 0-, 24-, 48-, and 72...
Article
To test the safety of a large intrathecal dose of human recombinant tissue plasminogen activator (rt-PA), 6 cynomolgous monkeys were given 10 mg of rt-PA (mean, 2.7 mg/kg) through an Ommaya reservoir after craniectomy and dissection of the basal cisterns. Bleeding occurred briefly at the incision in 2 animals; otherwise the clinical condition of al...
Article
Because of the naturally low fibrinolytic activity of CSF many erythrocytes entrapped in subarachnoid blood clot undergo hemolysis in situ, releasing vasogenic oxyhemoglobin (OxyHb) in high concentrations around the basal cerebral arteries. In order to promote more rapid clearance of erythrocytes from the basal subarachnoid cisterns we are currentl...
Article
The pharmacokinetics of recombinant murine interferon-gamma (rMuIFN-gamma) administered alone and in combination with recombinant hybrid human interferon-alpha (rHuIFN-alpha A/D-[Bgl]) were studied following intravenous (i.v.) and intramuscular (i.m.) injections into mice. The concomitant influence of these IFNs on splenic natural killer (NK) cell...
Article
The serum pharmacokinetics and the major organs of accumulation of recombinant human tumor necrosis factor-alpha (rHuTNF) were determined in BDF1 mice after intravenous and intramuscular administration. Serum concentrations of immunoreactive protein were determined by enzyme-linked immunosorbent assay, and radioactivity was quantitated by beta and...
Article
1. Topical application of 14C-viprostol, a synthetic prostaglandin E2 analogue, to laboratory animals resulted in a significant depot of radioactivity in the skin at the application site in all species studied: mouse, rat, guinea pig, rabbit and monkey, with longer residence times in the larger species. 2. The location of the 14C-label in the skin...
Article
We have investigated the in vitro and in vivo antitumor activities of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) against Meth A sarcoma. Meth A sarcoma cells were found to a) be relatively insensitive in vitro to rHuTNF-alpha, and b) express low numbers of TNF-alpha receptors. Intraperitoneally implanted Meth A sarcoma was insensi...
Chapter
The rational administration of any drug to a patient requires some knowledge of the anticipated efficacy and toxicity for a particular dose of that drug. When an understanding of how an individual patient will absorb and eliminate a drug is coupled together with knowledge of the pharmacologic effects of a given amount of the drug, a particular dose...
Article
Prior to the introduction of an intravenous dosage form for use in humans, prazosin pharmacokinetic studies emphasizing clearance, hepatic extraction, and bioavailability were carried out in dogs. Two such canine studies reported significantly different values for the oral bioavailability of prazosin. This study investigated the differences in praz...
Article
Tiodazosin is a recently developed compound that is currently undergoing investigation for use in hypertension. It is structurally and pharmacologically similar to prazosin, the prototype of the aminoquinazoline class of vasodilators. Lacking an intravenous dosage form for use in human subjects, our study concentrated on the determination of the bi...
Article
A new method for the determination of prazosin in human plasma, whole blood and urine is reported here. The method is simple, rapid, sensitive, involves no extraction steps and requires only 0.2 ml of biological sample.
Article
The pharmacokinetics of prazosin (Minipress) were studied in nine patients with NYHA Class 3 or 4 congestive heart failure and in five healthy controls. After a single 5 mg oral dose, plasma concentrations of prazosin, as reflected in the area under the plasma concentration-time curve (AUC) and prazosin plasma half-life, were approximately double i...
Article
The persistence of the hemodynamic effects of prazosin was studied in 12 patients with chronic congestive heart failure. Multidose evaluation involving five 5-mg doses showed the initial decrease in systemic vascular resistance and increase in cardiac index, stroke work index, and stroke volume index to be transient. Doubling the dose did not resto...

Network

Cited By

Projects

Project (1)