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C T Kirkpatrick

Publications and source records attributed to C T Kirkpatrick.

At least 19 recordsLinked to original sources
PubMed1996

Effect of food on the comparative pharmacokinetics of modified-release morphine tablet formulations: Oramorph SR and MST Continus.

The relative bioavailability and pharmacokinetic profiles of Oramorph SR (OSR) and MST Continus (MST), were evaluated by a randomized, four-way cross-over study in 24 healthy, male volunteers given single oral (30 mg) doses whilst fasting or after a high-fat breakfast. Mean Cmax, tmax, AUC (0,24h), AUC and tlag were significantly greater in fed compared with fasting subjects. Overall relative bioavailability of the two formulations (log AUC), was within the acceptable 80-125% limits for bioequivalence both fed and fasting. Mean fasting Cmax for OSR was greater than MST (P < 0.05) but there was no difference between formulations in mean fed Cmax. No statistically significant difference between OSR and MST was found for other parameters nor in the incidence of adverse events. These results suggest that OSR and MST are bioequivalent and that if patients were to transfer between formulations, dosage adjustment would be unnecessary, irrespective of their meal schedules or food intake.

Adolescent↗
PubMed1983

The quest for the inhibitory neurotransmitter in bovine tracheal smooth muscle.

The effect of inhibitory nerve stimulation on the mechanical, membrane potential and membrane conductance responses of isolated bovine tracheal smooth muscle has been studied. Membrane responses were measured in a sucrose-gap apparatus. In order to record inhibitory responses, it was necessary to increase tone in the preparation by applying a drug such as histamine. When tone was raised, repetitive field stimulation of intrinsic nerves caused depolarization and contraction, followed by relaxation and a suppression of histamine-induced slow waves. Hyperpolarization of the membrane was only seen following prolonged nerve stimulation, and there was no change in membrane conductance. The inhibitory effect of nerve stimulation was abolished by tetrodotoxin, but was not abolished by atropine, indomethacin, propranolol, naloxone or the purinergic blockers quinidine and theophylline. It was not satisfactorily mimicked by catecholamines, by gamma-amino-n-butyric acid (GABA) or by purines. Nerves with catecholamine fluorescence could not be found in the tracheal muscle layer. Neither adrenergic nor purinergic types of nerve terminal could be found in the tracheal muscle layer during ultrastructural examination of over one thousand nerve profiles. Vasoactive intestinal peptide (VIP) caused relaxation of the histamine-contracted tracheal muscle, suppressed the slow wave and caused slight hyperpolarization at higher concentrations, without affecting the membrane conductance. VIP was found in samples of tracheal muscle at a mean concentration of 1.95 ng/g. When the effluent solution flowing past isolated tracheal muscle strips was assayed for VIP, samples collected during inhibitory nerve stimulation had much higher concentrations of the peptide than samples collected before stimulation, after stimulation, or during stimulation in the presence of tetrodotoxin (10(-6) mol/l). The VIP content of the effluent during control periods was 73.8 pg/ml, and during stimulation was 167.5 pg/ml. It is suggested that VIP might be the non-adrenergic inhibitory neurotransmitter in bovine tracheal smooth muscle.

Acetylcholine↗
PubMed1980

Excitatory and inhibitory effects of histamine on molluscan neurons.

Histamine elicited depolarization (excitation) in some neurons and hyperpolarization (inhibition) in other neurons of the central nervous system of the marine mollusc, Onchidium verruculatum. The histamine sensitive region was along the axon at some distance from the soma. H1-receptor blockers (SA-97 and mepyramine) suppressed the excitatory (H1) response without affecting the inhibitory (H2) response, while H2-receptor blockers (burimamide and metiamide) suppressed the H2-response without affecting the H1-response. The H1-response was associated with a marked increase in membrane conductance and was blocked by removal of the external Na. The H2-response consisted of a hyperpolarization without much change in conductance, compared with the hyperpolarization of same amplitude produced by glutamate in the same neuron. Passive polarization of the membrane and reduction of Cl concentrations to 1/5-1/25 caused no significant change in H2-response. The H2-response was slightly suppressed in K-free saline. Thus, it seems difficult to account for the hyperpolarization only by an increase in K or Cl conductance. Complete removal of Na and addition of ouabain blocked the H2-response, suggesting a contribution of an electrogenic Na-pump to the hyperpolarization. However, in 20 mM Na saline with or without K, histamine still caused clear hyperpolarization. In this solution, the histamine response was not affected by ouabain. Although it is difficult to exclude the possibility that an increase in K conductance may be responsible for the hyperpolarization, it is tentatively proposed as a hypothesis that the H2-response involved some active transport mechanism, different from a ouabain-sensitive electrogenic Na-pump.

Animals↗
PubMed1980

An analysis of histamine-induced inhibitory response in molluscan neurons.

Mechanisms of the histamine-induced inhibitory response (the H2-response) in neurons of the marine mollusc Onchidium, were further investigated following the preceding paper. The H2-response in normal saline was blocked by ouabain, but the response recovered after a short exposure to Na-free solution containing ouabain. The recovery was only transient in the continuous presence of ouabain. When external Na was reduced to about 1/8 normal concentration (60 mM), the H2-response became sensitive to removal of external Ca, but insensitive to ouabain. The suppressing effect of Ca removal and the recovery by Ca readmission appeared very slowly. However, in about 1/3 normal Na concentration (150 mM) the H2-response was suppressed by removal of the Ca, only in the presence of ouabain. The Na-gradient may be regulated by the ouabain-insensitive transportk, such as a Na-Ca exchange in addition to the ouabain-sensitive Na-pump. The Na-Ca exchange probably dominates over the ouabain-sensitive Na-pump only when passive Na-influx is reduced in a low external Na concentration. The H2-response was markedly inhibited by DNP (5 X 10(-4)M) and cyanide (2 X 10(-3)M), while the hyperpolarization produced by glutamate, which was accompanied by a large reduction of membrane resistance, was not affected by these metabolic inhibitors. Over a wide range of external Na concentrations, the membrane potential was lower in presence than in the absence of external Ca. This may be explained by the hypothesis that there is an electrogenic Na-Ca exchange in which Ca-influx is coupled with Na-efflux. According to a similar hypothesis, the H2-response is produced by the transport system in which Ca-efflux is coupled with Na-influx and the system is controlled by the transmembrane Na gradient.

Animals↗
PubMed1977

A study of excitatory neuromuscular transmission in the bovine trachea.

1. The excitatory innervation of bovine tracheal smooth muscle has been studied with the sucrose-gap apparatus.2. Single 2 ms electrical stimuli applied to the whole tissue excited intrinsic nerves, and produced a small transient depolarization of the smooth muscle, the excitatory junction potential (e.j.p.). The e.j.p. caused a twitch-type contraction; twitches and e.j.p.s summated during repetitive stimulation but facilitation was not observed, and action potentials were never elicited.3. The effects of electrical stimulation could be abolished by atropine (5 x 10(-7) mol/l) and augmented by neostigmine (4 x 10(-6) mol/l), and were mimicked by exogenous acetylcholine (1.0 mug/ml).4. With the electron microscope, the density of innervation was found to be low (one axon per ninety smooth muscle cells). Axons were found in small groups in the clefts between bundles of cells, but no axons penetrated within the muscle bundles. Naked axon varicosities containing agranular vesicles were seen, but no axon approached within 200 nm of a smooth muscle cell.5. It is difficult to reconcile the sparsity of innervation with the dependence of the tissue on nerve excitation to initiate activity.

Acetylcholine↗